https://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_27&feed=atom&action=historyGlycoside Hydrolase Family 27 - Revision history2024-03-28T19:51:17ZRevision history for this page on the wikiMediaWiki 1.35.10https://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_27&diff=16552&oldid=prevHarry Brumer: Text replacement - "\^\^\^(.*)\^\^\^" to "$1"2021-12-18T21:16:18Z<p>Text replacement - "\^\^\^(.*)\^\^\^" to "<a href="/index.php?title=User:$1&action=edit&redlink=1" class="new" title="User:$1 (page does not exist)">$1</a>"</p>
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</table>Harry Brumerhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_27&diff=7506&oldid=prevHarry Brumer: updated CAZyDBlink2012-09-10T16:34:19Z<p>updated CAZyDBlink</p>
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</table>Harry Brumerhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_27&diff=6869&oldid=prevSpencer Williams at 01:28, 9 June 20112011-06-09T01:28:26Z<p></p>
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<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Substrate specificities ==</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Substrate specificities ==</div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>[[Glycoside hydrolases]] of family 27 possess a range of activities. <del class="diffchange diffchange-inline">Alpha</del>-<del class="diffchange diffchange-inline">galactosidase </del>activity has been observed in both bacterial and eukaryotic members of GH27, whereas <del class="diffchange diffchange-inline">alpha</del>-''N''-acetylgalactosaminidase activity has been observed in certain eukaryotic enzymes, including human, mouse, and chicken. Bacterial GH27 isomaltodextranases have also been identified. Notably, this family contains both human <del class="diffchange diffchange-inline">alpha</del>-galactosidase A and human <del class="diffchange diffchange-inline">alpha</del>-''N''-acetylgalactosaminidase (also known as <del class="diffchange diffchange-inline">alpha</del>-galactosidase B), defects in which produce the phenotypes associated with Fabry and Schindler lysosomal storage disorders, respectively <cite>4 5</cite>. Guided by protein tertiary structural analysis (''vide infra''), the substrate specificities of the human <del class="diffchange diffchange-inline">alpha</del>-galactosidase A and human <del class="diffchange diffchange-inline">alpha</del>-''N''-acetylgalactosaminidase have been interconverted by protein engineering <cite>Tomasic2010</cite>.</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>[[Glycoside hydrolases]] of family 27 possess a range of activities. <ins class="diffchange diffchange-inline">α</ins>-<ins class="diffchange diffchange-inline">Galactosidase </ins>activity has been observed in both bacterial and eukaryotic members of GH27, whereas <ins class="diffchange diffchange-inline">α</ins>-''N''-acetylgalactosaminidase activity has been observed in certain eukaryotic enzymes, including human, mouse, and chicken. Bacterial GH27 isomaltodextranases have also been identified. Notably, this family contains both human <ins class="diffchange diffchange-inline">α</ins>-galactosidase A and human <ins class="diffchange diffchange-inline">α</ins>-''N''-acetylgalactosaminidase (also known as <ins class="diffchange diffchange-inline">α</ins>-galactosidase B), defects in which produce the phenotypes associated with Fabry and Schindler lysosomal storage disorders, respectively <cite>4 5</cite>. Guided by protein tertiary structural analysis (''vide infra''), the substrate specificities of the human <ins class="diffchange diffchange-inline">α</ins>-galactosidase A and human <ins class="diffchange diffchange-inline">α</ins>-''N''-acetylgalactosaminidase have been interconverted by protein engineering <cite>Tomasic2010</cite>.</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Kinetics and Mechanism ==</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Kinetics and Mechanism ==</div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>Family GH27 <del class="diffchange diffchange-inline">alpha</del>-galactosidases are anomeric configuration-[[retaining]] enzymes, as first demonstrated by proton NMR studies of the hydrolysis of ''p''-nitrophenyl <del class="diffchange diffchange-inline">alpha</del>-galactopyranoside by an <del class="diffchange diffchange-inline">alpha</del>-galactosidase isolated from the white-rot fungus ''Phanerochaete chrysosporium'' <cite>1</cite>. GH27 enzymes are thus expected to use a classical [[Koshland double-displacement mechanism]] <cite>6</cite>, which involves the formation of a covalent glycosyl-enzyme [[intermediate]] <cite>7</cite>. As predicted based on their common clanship in Clan GH-D, [[Glycoside Hydrolase Family 36 (GH36)]] enzymes also operate through the same "[[retaining]]" mechanism <cite>8</cite>.</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>Family GH27 <ins class="diffchange diffchange-inline">α</ins>-galactosidases are anomeric configuration-[[retaining]] enzymes, as first demonstrated by proton NMR studies of the hydrolysis of ''p''-nitrophenyl <ins class="diffchange diffchange-inline">α</ins>-galactopyranoside by an <ins class="diffchange diffchange-inline">α</ins>-galactosidase isolated from the white-rot fungus ''Phanerochaete chrysosporium'' <cite>1</cite>. GH27 enzymes are thus expected to use a classical [[Koshland double-displacement mechanism]] <cite>6</cite>, which involves the formation of a covalent glycosyl-enzyme [[intermediate]] <cite>7</cite>. As predicted based on their common clanship in Clan GH-D, [[Glycoside Hydrolase Family 36 (GH36)]] enzymes also operate through the same "[[retaining]]" mechanism <cite>8</cite>.</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Catalytic Residues ==</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Catalytic Residues ==</div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>The conserved amino acid sidechain that functions as the [[catalytic nucleophile]] in GH27 has been identified in two different eukaryotic family members by mechanism-based labelling, proteolytic digestion, and mass spectrometric analysis. Identification of Asp-130 in the YLKY'''D'''NC sequence fragment of the ''Phanerochaete chrysosporium'' <del class="diffchange diffchange-inline">alpha</del>-galactosidase by labelling with 2',4',6'-trinitrophenyl 2-deoxy-2,2-difluoro-<del class="diffchange diffchange-inline">alpha</del>-D-''lyxo''-hexopyranoside ("2,2-difluoro-<del class="diffchange diffchange-inline">alpha</del>-galactosyl picrate") <cite>2</cite> only slightly predated the identification of the same conserved aspartate in the green coffee bean <del class="diffchange diffchange-inline">alpha</del>-galactosidase (Asp-145 in the sequence LKY'''D'''NCNNN) using 5-fluoro-<del class="diffchange diffchange-inline">alpha</del>-D-galactopyranosyl fluoride as a labelling agent <cite>9</cite>. The subsequent observation of a trapped covalent 2-deoxy-2,2-difluorogalactosyl-enzyme intermediate human (''Homo sapiens'') <del class="diffchange diffchange-inline">alpha</del>-galactosidase A on Asp170 of that enzyme provided further "visual" confirmation of the identity of the [[catalytic nucleophile]] in this family <cite>GuceJBC2010</cite>.</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>The conserved amino acid sidechain that functions as the [[catalytic nucleophile]] in GH27 has been identified in two different eukaryotic family members by mechanism-based labelling, proteolytic digestion, and mass spectrometric analysis. Identification of Asp-130 in the YLKY'''D'''NC sequence fragment of the ''Phanerochaete chrysosporium'' <ins class="diffchange diffchange-inline">α</ins>-galactosidase by labelling with 2',4',6'-trinitrophenyl 2-deoxy-2,2-difluoro-<ins class="diffchange diffchange-inline">α</ins>-D-''lyxo''-hexopyranoside ("2,2-difluoro-<ins class="diffchange diffchange-inline">α</ins>-galactosyl picrate") <cite>2</cite> only slightly predated the identification of the same conserved aspartate in the green coffee bean <ins class="diffchange diffchange-inline">α</ins>-galactosidase (Asp-145 in the sequence LKY'''D'''NCNNN) using 5-fluoro-<ins class="diffchange diffchange-inline">α</ins>-D-galactopyranosyl fluoride as a labelling agent <cite>9</cite>. The subsequent observation of a trapped covalent 2-deoxy-2,2-difluorogalactosyl-enzyme intermediate human (''Homo sapiens'') <ins class="diffchange diffchange-inline">α</ins>-galactosidase A on Asp170 of that enzyme provided further "visual" confirmation of the identity of the [[catalytic nucleophile]] in this family <cite>GuceJBC2010</cite>.</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>The [[general acid/base]] residue in this family was first identified by X-ray structural analysis of the chicken (''Gallus gallus'') ''N''-acetylgalactosaminidase in complex with ''N''-acetylgalactosamine <cite>3</cite>. The position of the product within the enzyme active site indicated that Asp-201 in the sequence CNLWRNYD'''D'''IQDSW was the obvious candidate to fulfill this role. Subsequent product complexes of the rice <del class="diffchange diffchange-inline">alpha</del>-galactosidase <cite>11</cite>, human <del class="diffchange diffchange-inline">alpha</del>-galactosidase A <cite>10</cite>, and the ''Hypocrea jecorina'' (née ''Trichoderma reesei'') <del class="diffchange diffchange-inline">alpha</del>-galactosidase <cite>12</cite> have similarly implicated the homologous residue in these enzymes in catalysis.</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>The [[general acid/base]] residue in this family was first identified by X-ray structural analysis of the chicken (''Gallus gallus'') ''N''-acetylgalactosaminidase in complex with ''N''-acetylgalactosamine <cite>3</cite>. The position of the product within the enzyme active site indicated that Asp-201 in the sequence CNLWRNYD'''D'''IQDSW was the obvious candidate to fulfill this role. Subsequent product complexes of the rice <ins class="diffchange diffchange-inline">α</ins>-galactosidase <cite>11</cite>, human <ins class="diffchange diffchange-inline">α</ins>-galactosidase A <cite>10</cite>, and the ''Hypocrea jecorina'' (née ''Trichoderma reesei'') <ins class="diffchange diffchange-inline">α</ins>-galactosidase <cite>12</cite> have similarly implicated the homologous residue in these enzymes in catalysis.</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>Interestingly, of the over 200 known point mutations in human <del class="diffchange diffchange-inline">alpha</del>-galactosidase A that lead to Fabry disease, very few involve the catalytic residues <cite>3 4 10</cite>. While many mutations are thought to disrupt the hydrophobic core of the enzyme or otherwise disrupt protein folding, only the D170V, D170H, and D231N genotypic variants are known, with obvious catalytic implications <cite>4 10</cite>. Several other mutations are known to affect key active site structural or substrate-binding residues in human <del class="diffchange diffchange-inline">alpha</del>-galactosidase A <cite>10</cite>. Whereas Fabry disease is X-linked and therefore comparatively more common, the autosomal recessive Schindler disease is rare <cite>4</cite>. Comparative analysis using the structurally similar human <del class="diffchange diffchange-inline">alpha</del>-galactosidase A <cite>10</cite> and chicken ''N''-acetylgalactosaminidase <cite>3</cite> enzymes has indicated that none of the few known mutations in the human GH27 ''N''-acetylgalactosaminidase occur in the catalytic nor active site residues <cite>4</cite>.</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>Interestingly, of the over 200 known point mutations in human <ins class="diffchange diffchange-inline">α</ins>-galactosidase A that lead to Fabry disease, very few involve the catalytic residues <cite>3 4 10</cite>. While many mutations are thought to disrupt the hydrophobic core of the enzyme or otherwise disrupt protein folding, only the D170V, D170H, and D231N genotypic variants are known, with obvious catalytic implications <cite>4 10</cite>. Several other mutations are known to affect key active site structural or substrate-binding residues in human <ins class="diffchange diffchange-inline">α</ins>-galactosidase A <cite>10</cite>. Whereas Fabry disease is X-linked and therefore comparatively more common, the autosomal recessive Schindler disease is rare <cite>4</cite>. Comparative analysis using the structurally similar human <ins class="diffchange diffchange-inline">α</ins>-galactosidase A <cite>10</cite> and chicken ''N''-acetylgalactosaminidase <cite>3</cite> enzymes has indicated that none of the few known mutations in the human GH27 ''N''-acetylgalactosaminidase occur in the catalytic nor active site residues <cite>4</cite>.</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Three-dimensional structures ==</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Three-dimensional structures ==</div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>Published in 2002, the 3-D structure of the chicken (''Gallus gallus'') ''N''-acetylgalactosaminidase solved by Garman ''et al.'' using X-ray crystallography (1.9 Å resolution) represented the first structure of an enzyme from GH27, and indeed [[Sequence-based classification of glycoside hydrolases|Clan]] GH-D <cite>3</cite>. Futhermore, the simultaneous solution of an enzyme-product complex (2.4 Å), was instrumental in defining the catalytic acid/base residue in this GH family and clan <cite>3</cite>, as described above. Soon thereafter, structures of the rice (''Oryza sativa'') <del class="diffchange diffchange-inline">alpha</del>-galactosidase (2003) <cite>11</cite>, human (''Homo sapiens'') <del class="diffchange diffchange-inline">alpha</del>-galactosidase A (2004) <cite>10</cite>, and ''Hypocrea jecorina'' (née ''Trichoderma reesei'') <del class="diffchange diffchange-inline">alpha</del>-galactosidase (2004) <cite>12</cite> were presented in both free and product-complexed forms. All of these structures indicated that GH27 enzymes are comprised of an N-terminal (<del class="diffchange diffchange-inline">alpha</del>/<del class="diffchange diffchange-inline">beta</del>)8 (TIM) barrel domain and a C-terminal anti-parallel <del class="diffchange diffchange-inline">beta</del>-jellyroll domain, the former of which contains the enzyme catalytic center composed by loop residues at the ends of <del class="diffchange diffchange-inline">beta </del>strands 1-7.</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>Published in 2002, the 3-D structure of the chicken (''Gallus gallus'') ''N''-acetylgalactosaminidase solved by Garman ''et al.'' using X-ray crystallography (1.9 Å resolution) represented the first structure of an enzyme from GH27, and indeed [[Sequence-based classification of glycoside hydrolases|Clan]] GH-D <cite>3</cite>. Futhermore, the simultaneous solution of an enzyme-product complex (2.4 Å), was instrumental in defining the catalytic acid/base residue in this GH family and clan <cite>3</cite>, as described above. Soon thereafter, structures of the rice (''Oryza sativa'') <ins class="diffchange diffchange-inline">α</ins>-galactosidase (2003) <cite>11</cite>, human (''Homo sapiens'') <ins class="diffchange diffchange-inline">α</ins>-galactosidase A (2004) <cite>10</cite>, and ''Hypocrea jecorina'' (née ''Trichoderma reesei'') <ins class="diffchange diffchange-inline">α</ins>-galactosidase (2004) <cite>12</cite> were presented in both free and product-complexed forms. All of these structures indicated that GH27 enzymes are comprised of an N-terminal (<ins class="diffchange diffchange-inline">α</ins>/<ins class="diffchange diffchange-inline">β</ins>)<ins class="diffchange diffchange-inline"><sub></ins>8<ins class="diffchange diffchange-inline"></sub> </ins>(TIM) barrel domain and a C-terminal anti-parallel <ins class="diffchange diffchange-inline">β</ins>-jellyroll domain, the former of which contains the enzyme catalytic center composed by loop residues at the ends of <ins class="diffchange diffchange-inline">β </ins>strands 1-7.</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>In 2010, Garman and co-workers published an ensemble of tertiary structures of the human <del class="diffchange diffchange-inline">alpha</del>-galactosidase A, which included a trapped covalent 2-deoxy-2,2-difluorogalactosyl-enzyme [[intermediate]] in an <sup>1</sup>''S''<sub>3</sub> skew boat [[conformational itinerary|conformation]] <cite>GuceJBC2010</cite>. Together with native, substrate-bound (E&bull;S, Michaelis complex), and product-bound (E&bull;P) structures, this work provided the first complete analysis of substrate distortion along the enzyme reaction coordinate in GH27. Thus, GH27 enzymes use a</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>In 2010, Garman and co-workers published an ensemble of tertiary structures of the human <ins class="diffchange diffchange-inline">α</ins>-galactosidase A, which included a trapped covalent 2-deoxy-2,2-difluorogalactosyl-enzyme [[intermediate]] in an <sup>1</sup>''S''<sub>3</sub> skew boat [[conformational itinerary|conformation]] <cite>GuceJBC2010</cite>. Together with native, substrate-bound (E&bull;S, Michaelis complex), and product-bound (E&bull;P) structures, this work provided the first complete analysis of substrate distortion along the enzyme reaction coordinate in GH27. Thus, GH27 enzymes use a</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><sup>4</sup>''C''<sub>1</sub> &harr; (<sup>4</sup>''H''<sub>3</sub>)<sup>&Dagger;</sup> &harr; <sup>1</sup>''S''<sub>3</sub> &harr; (<sup>4</sup>''H''<sub>3</sub>)<sup>&Dagger;</sup> &harr; <sup>4</sup>''C''<sub>1</sub></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><sup>4</sup>''C''<sub>1</sub> &harr; (<sup>4</sup>''H''<sub>3</sub>)<sup>&Dagger;</sup> &harr; <sup>1</sup>''S''<sub>3</sub> &harr; (<sup>4</sup>''H''<sub>3</sub>)<sup>&Dagger;</sup> &harr; <sup>4</sup>''C''<sub>1</sub></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>[[conformational itinerary]]. This is the same itinerary employed by [[GH31]] enzymes (also of Clan GH-D, ''vide infra''), while the <del class="diffchange diffchange-inline">alpha</del>-<u>{{Smallcaps|l}}</u>-fucosidases of [[GH29]] use the mirror-image itinerary:</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>[[conformational itinerary]]. This is the same itinerary employed by [[GH31]] enzymes (also of Clan GH-D, ''vide infra''), while the <ins class="diffchange diffchange-inline">α</ins>-<u>{{Smallcaps|l}}</u>-fucosidases of [[GH29]] use the mirror-image itinerary:</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><sup>1</sup>''C''<sub>4</sub> &harr; (<sup>3</sup>''H''<sub>4</sub>)<sup>&Dagger;</sup> &harr; <sup>3</sup>''S''<sub>1</sub> &harr; (<sup>3</sup>''H''<sub>4</sub>)<sup>&Dagger;</sup> &harr; <sup>1</sup>''C''<sub>4</sub> (see <cite>LammertsJACS2010</cite> for a full discussion).</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><sup>1</sup>''C''<sub>4</sub> &harr; (<sup>3</sup>''H''<sub>4</sub>)<sup>&Dagger;</sup> &harr; <sup>3</sup>''S''<sub>1</sub> &harr; (<sup>3</sup>''H''<sub>4</sub>)<sup>&Dagger;</sup> &harr; <sup>1</sup>''C''<sub>4</sub> (see <cite>LammertsJACS2010</cite> for a full discussion).</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>The known overall structures of GH27 enzymes are all highly conserved and the N-terminal domains are all closely superimposable, with minor exceptions including the ''H. jecorina'' (''T. reesei'') <del class="diffchange diffchange-inline">alpha</del>-galactosidase <cite>12</cite>, which contains a 40 amino acid insertion in loop <del class="diffchange diffchange-inline">beta4</del>-<del class="diffchange diffchange-inline">alpha4</del>, and the animal enzymes <cite>3 10</cite>, which contain a short 10 residue insertion in the <del class="diffchange diffchange-inline">alpha1</del>-<del class="diffchange diffchange-inline">beta1 </del>loop <cite>4</cite>. The C-terminal domains, although similar, are less well conserved, both at the primary and tertiary structural levels <cite>4</cite>. In keeping with the ''[[exo]]'' mode of action of these enzymes, which cleave <del class="diffchange diffchange-inline">alpha</del>-Gal from the non-reducing termini of their substrates, the active sites are pocket-shaped <cite>3 11 12 10</cite>. Specificity for the 2-hydroxyl substituent, in the case of <del class="diffchange diffchange-inline">alpha</del>-galactosidases in the family, and the 2-deoxy-2-''N''-acetyl substituent, in the case of the <del class="diffchange diffchange-inline">alpha</del>-''N''-acetylgalactosaminidases, is dictated by the presence of correspondingly large or small active-site binding residues, respectively <cite>10</cite> (reviewed in <cite>4</cite>). Based on these observations, phylogenetic analysis has been presented which may have some power to predict specificity within GH27 <cite>10</cite>.</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>The known overall structures of GH27 enzymes are all highly conserved and the N-terminal domains are all closely superimposable, with minor exceptions including the ''H. jecorina'' (''T. reesei'') <ins class="diffchange diffchange-inline">α</ins>-galactosidase <cite>12</cite>, which contains a 40 amino acid insertion in loop <ins class="diffchange diffchange-inline">β4</ins>-<ins class="diffchange diffchange-inline">α4</ins>, and the animal enzymes <cite>3 10</cite>, which contain a short 10 residue insertion in the <ins class="diffchange diffchange-inline">α1</ins>-<ins class="diffchange diffchange-inline">β1 </ins>loop <cite>4</cite>. The C-terminal domains, although similar, are less well conserved, both at the primary and tertiary structural levels <cite>4</cite>. In keeping with the ''[[exo]]'' mode of action of these enzymes, which cleave <ins class="diffchange diffchange-inline">α</ins>-Gal from the non-reducing termini of their substrates, the active sites are pocket-shaped <cite>3 11 12 10</cite>. Specificity for the 2-hydroxyl substituent, in the case of <ins class="diffchange diffchange-inline">α</ins>-galactosidases in the family, and the 2-deoxy-2-''N''-acetyl substituent, in the case of the <ins class="diffchange diffchange-inline">α</ins>-''N''-acetylgalactosaminidases, is dictated by the presence of correspondingly large or small active-site binding residues, respectively <cite>10</cite> (reviewed in <cite>4</cite>). Based on these observations, phylogenetic analysis has been presented which may have some power to predict specificity within GH27 <cite>10</cite>.</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>As predicted by their common membership in Clan GH-D, [[GH36]] enzymes likewise present active sites on (<del class="diffchange diffchange-inline">alpha</del>/<del class="diffchange diffchange-inline">beta</del>)8 barrel domains <cite>8</cite>. [[GH36]] enzymes also contain a related C-terminal <del class="diffchange diffchange-inline">beta</del>-sheet domain, in addition to a large <del class="diffchange diffchange-inline">beta</del>-supersandwich N-terminal domain not found in GH27 enzymes <cite>8</cite>. Structural analysis of a [[GH31]] enzyme has led to the addition of this family to Clan GH-D <cite>13</cite>.</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>As predicted by their common membership in Clan GH-D, [[GH36]] enzymes likewise present active sites on (<ins class="diffchange diffchange-inline">α</ins>/<ins class="diffchange diffchange-inline">β</ins>)<ins class="diffchange diffchange-inline"><sub></ins>8<ins class="diffchange diffchange-inline"></sub> </ins>barrel domains <cite>8</cite>. [[GH36]] enzymes also contain a related C-terminal <ins class="diffchange diffchange-inline">β</ins>-sheet domain, in addition to a large <ins class="diffchange diffchange-inline">β</ins>-supersandwich N-terminal domain not found in GH27 enzymes <cite>8</cite>. Structural analysis of a [[GH31]] enzyme has led to the addition of this family to Clan GH-D <cite>13</cite>.</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Family Firsts ==</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Family Firsts ==</div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>;First sterochemistry determination: Retention of anomeric stereochemistry demonstrated by H-1 NMR for the main <del class="diffchange diffchange-inline">alpha</del>-galactosidase from the white-rot fungus ''Phanerochaete chrysosporium'' <cite>1</cite>.</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>;First sterochemistry determination: Retention of anomeric stereochemistry demonstrated by H-1 NMR for the main <ins class="diffchange diffchange-inline">α</ins>-galactosidase from the white-rot fungus ''Phanerochaete chrysosporium'' <cite>1</cite>.</div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>;First [[catalytic nucleophile]] identification: ''Phanerochaete chrysosporium'' <del class="diffchange diffchange-inline">alpha</del>-galactosidase by mechanism-based labelling with 2',4',6'-trinitrophenyl 2-deoxy-2,2-difluoro-<del class="diffchange diffchange-inline">alpha</del>-D-''lyxo''-hexopyranoside ("2,2-difluoro-<del class="diffchange diffchange-inline">alpha</del>-galactosyl picrate"), pepsin digestion, and mass spectrometry <cite>2</cite>.</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>;First [[catalytic nucleophile]] identification: ''Phanerochaete chrysosporium'' <ins class="diffchange diffchange-inline">α</ins>-galactosidase by mechanism-based labelling with 2',4',6'-trinitrophenyl 2-deoxy-2,2-difluoro-<ins class="diffchange diffchange-inline">α</ins>-D-''lyxo''-hexopyranoside ("2,2-difluoro-<ins class="diffchange diffchange-inline">α</ins>-galactosyl picrate"), pepsin digestion, and mass spectrometry <cite>2</cite>.</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>;First [[general acid/base]] residue identification: Chicken (''Gallus gallus'') ''N''-acetylgalactosaminidase by X-ray structural analysis of an enzyme-''N''-acetylgalactosamine complex <cite>3</cite>.</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>;First [[general acid/base]] residue identification: Chicken (''Gallus gallus'') ''N''-acetylgalactosaminidase by X-ray structural analysis of an enzyme-''N''-acetylgalactosamine complex <cite>3</cite>.</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>;First 3-D structure: Chicken ''N''-acetylgalactosaminidase, both free enzyme and in complex with ''N''-acetylgalactosamine <cite>3</cite>.</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>;First 3-D structure: Chicken ''N''-acetylgalactosaminidase, both free enzyme and in complex with ''N''-acetylgalactosamine <cite>3</cite>.</div></td></tr>
</table>Spencer Williamshttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_27&diff=5262&oldid=prevHarry Brumer at 07:36, 30 July 20102010-07-30T07:36:38Z<p></p>
<table class="diff diff-contentalign-left diff-editfont-monospace" data-mw="interface">
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 07:36, 30 July 2010</td>
</tr><tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l26" >Line 26:</td>
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<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Substrate specificities ==</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Substrate specificities ==</div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>[[Glycoside hydrolases]] of family 27 possess a range of activities. Alpha-galactosidase activity has been observed in both bacterial and eukaryotic members of GH27, whereas alpha-''N''-acetylgalactosaminidase activity has been observed in certain eukaryotic enzymes, including human, mouse, and chicken. Bacterial GH27 isomaltodextranases have also been identified. Notably, this family contains both human alpha-galactosidase A and human alpha-''N''-acetylgalactosaminidase (also known as alpha-galactosidase B), defects in which produce the phenotypes associated with Fabry and Schindler lysosomal storage disorders, respectively <cite>4 5</cite>.</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>[[Glycoside hydrolases]] of family 27 possess a range of activities. Alpha-galactosidase activity has been observed in both bacterial and eukaryotic members of GH27, whereas alpha-''N''-acetylgalactosaminidase activity has been observed in certain eukaryotic enzymes, including human, mouse, and chicken. Bacterial GH27 isomaltodextranases have also been identified. Notably, this family contains both human alpha-galactosidase A and human alpha-''N''-acetylgalactosaminidase (also known as alpha-galactosidase B), defects in which produce the phenotypes associated with Fabry and Schindler lysosomal storage disorders, respectively <cite>4 5<ins class="diffchange diffchange-inline"></cite>. Guided by protein tertiary structural analysis (''vide infra''), the substrate specificities of the human alpha-galactosidase A and human alpha-''N''-acetylgalactosaminidase have been interconverted by protein engineering <cite>Tomasic2010</ins></cite>.</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Kinetics and Mechanism ==</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Kinetics and Mechanism ==</div></td></tr>
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<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>#GuceJBC2010 pmid=19940122</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>#GuceJBC2010 pmid=19940122</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>#LammertsJACS2010 pmid=20092273</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>#LammertsJACS2010 pmid=20092273</div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">#Tomasic2010 pmid=20444686</ins></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div></biblio></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div></biblio></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><!-- DO NOT REMOVE THIS CATEGORY TAG! --></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><!-- DO NOT REMOVE THIS CATEGORY TAG! --></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Category:Glycoside Hydrolase Families|GH027]]</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Category:Glycoside Hydrolase Families|GH027]]</div></td></tr>
</table>Harry Brumerhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_27&diff=4999&oldid=prevSpencer Williams: /* Three-dimensional structures */2010-06-19T23:53:25Z<p><span dir="auto"><span class="autocomment">Three-dimensional structures</span></span></p>
<table class="diff diff-contentalign-left diff-editfont-monospace" data-mw="interface">
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">← Older revision</td>
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 23:53, 19 June 2010</td>
</tr><tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l39" >Line 39:</td>
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<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Three-dimensional structures ==</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Three-dimensional structures ==</div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>Published in 2002, the 3-D structure of the chicken (''Gallus gallus'') ''N''-acetylgalactosaminidase solved by Garman ''et al.'' using X-ray crystallography (1.9 Å resolution) represented the first structure of an enzyme from GH27, and indeed Clan GH-D <cite>3</cite>. Futhermore, the simultaneous solution of an enzyme-product complex (2.4 Å), was instrumental in defining the catalytic acid/base residue in this GH family and clan <cite>3</cite>, as described above. Soon thereafter, structures of the rice (''Oryza sativa'') alpha-galactosidase (2003) <cite>11</cite>, human (''Homo sapiens'') alpha-galactosidase A (2004) <cite>10</cite>, and ''Hypocrea jecorina'' (née ''Trichoderma reesei'') alpha-galactosidase (2004) <cite>12</cite> were presented in both free and product-complexed forms. All of these structures indicated that GH27 enzymes are comprised of an N-terminal (alpha/beta)8 (TIM) barrel domain and a C-terminal anti-parallel beta-jellyroll domain, the former of which contains the enzyme catalytic center composed by loop residues at the ends of beta strands 1-7.</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>Published in 2002, the 3-D structure of the chicken (''Gallus gallus'') ''N''-acetylgalactosaminidase solved by Garman ''et al.'' using X-ray crystallography (1.9 Å resolution) represented the first structure of an enzyme from GH27, and indeed <ins class="diffchange diffchange-inline">[[Sequence-based classification of glycoside hydrolases|</ins>Clan<ins class="diffchange diffchange-inline">]] </ins>GH-D <cite>3</cite>. Futhermore, the simultaneous solution of an enzyme-product complex (2.4 Å), was instrumental in defining the catalytic acid/base residue in this GH family and clan <cite>3</cite>, as described above. Soon thereafter, structures of the rice (''Oryza sativa'') alpha-galactosidase (2003) <cite>11</cite>, human (''Homo sapiens'') alpha-galactosidase A (2004) <cite>10</cite>, and ''Hypocrea jecorina'' (née ''Trichoderma reesei'') alpha-galactosidase (2004) <cite>12</cite> were presented in both free and product-complexed forms. All of these structures indicated that GH27 enzymes are comprised of an N-terminal (alpha/beta)8 (TIM) barrel domain and a C-terminal anti-parallel beta-jellyroll domain, the former of which contains the enzyme catalytic center composed by loop residues at the ends of beta strands 1-7.</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>In 2010, Garman and co-workers published an ensemble of tertiary structures of the human alpha-galactosidase A, which included a trapped covalent 2-deoxy-2,2-difluorogalactosyl-enzyme intermediate in an <sup>1</sup>''S''<sub>3</sub> skew boat conformation <cite>GuceJBC2010</cite>. Together with native, substrate-bound (E&bull;S, Michaelis complex), and product-bound (E&bull;P) structures, this work provided the first complete analysis of substrate distortion along the enzyme reaction coordinate in GH27. Thus, GH27 enzymes use a</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>In 2010, Garman and co-workers published an ensemble of tertiary structures of the human alpha-galactosidase A, which included a trapped covalent 2-deoxy-2,2-difluorogalactosyl-enzyme <ins class="diffchange diffchange-inline">[[</ins>intermediate<ins class="diffchange diffchange-inline">]] </ins>in an <sup>1</sup>''S''<sub>3</sub> skew boat <ins class="diffchange diffchange-inline">[[conformational itinerary|</ins>conformation<ins class="diffchange diffchange-inline">]] </ins><cite>GuceJBC2010</cite>. Together with native, substrate-bound (E&bull;S, Michaelis complex), and product-bound (E&bull;P) structures, this work provided the first complete analysis of substrate distortion along the enzyme reaction coordinate in GH27. Thus, GH27 enzymes use a</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><sup>4</sup>''C''<sub>1</sub> &harr; (<sup>4</sup>''H''<sub>3</sub>)<sup>&Dagger;</sup> &harr; <sup>1</sup>''S''<sub>3</sub> &harr; (<sup>4</sup>''H''<sub>3</sub>)<sup>&Dagger;</sup> &harr; <sup>4</sup>''C''<sub>1</sub></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><sup>4</sup>''C''<sub>1</sub> &harr; (<sup>4</sup>''H''<sub>3</sub>)<sup>&Dagger;</sup> &harr; <sup>1</sup>''S''<sub>3</sub> &harr; (<sup>4</sup>''H''<sub>3</sub>)<sup>&Dagger;</sup> &harr; <sup>4</sup>''C''<sub>1</sub></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>conformational itinerary. This is the same itinerary employed by [[GH31]] enzymes (also of Clan GH-D, ''vide infra''), while the alpha-<u>{{Smallcaps|l}}</u>-fucosidases of [[GH29]] use the mirror-image itinerary:</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline">[[</ins>conformational itinerary<ins class="diffchange diffchange-inline">]]</ins>. This is the same itinerary employed by [[GH31]] enzymes (also of Clan GH-D, ''vide infra''), while the alpha-<u>{{Smallcaps|l}}</u>-fucosidases of [[GH29]] use the mirror-image itinerary:</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><sup>1</sup>''C''<sub>4</sub> &harr; (<sup>3</sup>''H''<sub>4</sub>)<sup>&Dagger;</sup> &harr; <sup>3</sup>''S''<sub>1</sub> &harr; (<sup>3</sup>''H''<sub>4</sub>)<sup>&Dagger;</sup> &harr; <sup>1</sup>''C''<sub>4</sub> (see <cite>LammertsJACS2010</cite> for a full discussion).</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><sup>1</sup>''C''<sub>4</sub> &harr; (<sup>3</sup>''H''<sub>4</sub>)<sup>&Dagger;</sup> &harr; <sup>3</sup>''S''<sub>1</sub> &harr; (<sup>3</sup>''H''<sub>4</sub>)<sup>&Dagger;</sup> &harr; <sup>1</sup>''C''<sub>4</sub> (see <cite>LammertsJACS2010</cite> for a full discussion).</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>The known overall structures of GH27 enzymes are all highly conserved and the N-terminal domains are all closely superimposable, with minor exceptions including the ''H. jecorina'' (''T. reesei'') alpha-galactosidase <cite>12</cite>, which contains a 40 amino acid insertion in loop beta4-alpha4, and the animal enzymes <cite>3 10</cite>, which contain a short 10 residue insertion in the alpha1-beta1 loop <cite>4</cite>. The C-terminal domains, although similar, are less well conserved, both at the primary and tertiary structural levels <cite>4</cite>. In keeping with the ''[[exo]]'' mode of action of these enzymes, which cleave alpha-Gal from the non-reducing <del class="diffchange diffchange-inline">terminii </del>of their substrates, the active sites are pocket-shaped <cite>3 11 12 10</cite>. Specificity for the 2-hydroxyl substituent, in the case of alpha-galactosidases in the family, and the 2-deoxy-2-''N''-acetyl substituent, in the case of the alpha-''N''-acetylgalactosaminidases, is dictated by the presence of correspondingly large or small active-site binding residues, respectively <cite>10</cite> (reviewed in <cite>4</cite>). Based on these observations, phylogenetic analysis has been presented which may have some power to predict specificity within GH27 <cite>10</cite>.</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>The known overall structures of GH27 enzymes are all highly conserved and the N-terminal domains are all closely superimposable, with minor exceptions including the ''H. jecorina'' (''T. reesei'') alpha-galactosidase <cite>12</cite>, which contains a 40 amino acid insertion in loop beta4-alpha4, and the animal enzymes <cite>3 10</cite>, which contain a short 10 residue insertion in the alpha1-beta1 loop <cite>4</cite>. The C-terminal domains, although similar, are less well conserved, both at the primary and tertiary structural levels <cite>4</cite>. In keeping with the ''[[exo]]'' mode of action of these enzymes, which cleave alpha-Gal from the non-reducing <ins class="diffchange diffchange-inline">termini </ins>of their substrates, the active sites are pocket-shaped <cite>3 11 12 10</cite>. Specificity for the 2-hydroxyl substituent, in the case of alpha-galactosidases in the family, and the 2-deoxy-2-''N''-acetyl substituent, in the case of the alpha-''N''-acetylgalactosaminidases, is dictated by the presence of correspondingly large or small active-site binding residues, respectively <cite>10</cite> (reviewed in <cite>4</cite>). Based on these observations, phylogenetic analysis has been presented which may have some power to predict specificity within GH27 <cite>10</cite>.</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>As predicted by their common membership in Clan GH-D, [[GH36]] enzymes likewise present active sites on (alpha/beta)8 barrel domains <cite>8</cite>. [[GH36]] enzymes also contain a related C-terminal beta-sheet domain, in addition to a large beta-supersandwich N-terminal domain not found in GH27 enzymes <cite>8</cite>. Structural analysis of a [[GH31]] enzyme has led to the addition of this family to Clan GH-D <cite>13</cite>.</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>As predicted by their common membership in Clan GH-D, [[GH36]] enzymes likewise present active sites on (alpha/beta)8 barrel domains <cite>8</cite>. [[GH36]] enzymes also contain a related C-terminal beta-sheet domain, in addition to a large beta-supersandwich N-terminal domain not found in GH27 enzymes <cite>8</cite>. Structural analysis of a [[GH31]] enzyme has led to the addition of this family to Clan GH-D <cite>13</cite>.</div></td></tr>
</table>Spencer Williamshttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_27&diff=4162&oldid=prevHarry Brumer: /* Three-dimensional structures */2010-02-28T09:50:20Z<p><span dir="auto"><span class="autocomment">Three-dimensional structures</span></span></p>
<table class="diff diff-contentalign-left diff-editfont-monospace" data-mw="interface">
<col class="diff-marker" />
<col class="diff-content" />
<col class="diff-marker" />
<col class="diff-content" />
<tr class="diff-title" lang="en-CA">
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">← Older revision</td>
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 09:50, 28 February 2010</td>
</tr><tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l43" >Line 43:</td>
<td colspan="2" class="diff-lineno">Line 43:</td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>In 2010, Garman and co-workers published an ensemble of tertiary structures of the human alpha-galactosidase A, which included a trapped covalent 2-deoxy-2,2-difluorogalactosyl-enzyme intermediate in an <sup>1</sup>''S''<sub>3</sub> skew boat conformation <cite>GuceJBC2010</cite>. Together with native, substrate-bound (E&bull;S, Michaelis complex), and product-bound (E&bull;P) structures, this work provided the first complete analysis of substrate distortion along the enzyme reaction coordinate in GH27. Thus, GH27 enzymes use a</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>In 2010, Garman and co-workers published an ensemble of tertiary structures of the human alpha-galactosidase A, which included a trapped covalent 2-deoxy-2,2-difluorogalactosyl-enzyme intermediate in an <sup>1</sup>''S''<sub>3</sub> skew boat conformation <cite>GuceJBC2010</cite>. Together with native, substrate-bound (E&bull;S, Michaelis complex), and product-bound (E&bull;P) structures, this work provided the first complete analysis of substrate distortion along the enzyme reaction coordinate in GH27. Thus, GH27 enzymes use a</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><sup>4</sup>''C''<sub>1</sub> &harr; (<sup>4</sup>''H''<sub>3</sub>)<sup>&Dagger;</sup> &harr; <sup>1</sup>''S''<sub>3</sub> &harr; (<sup>4</sup>''H''<sub>3</sub>)<sup>&Dagger;</sup> &harr; <sup>4</sup>''C''<sub>1</sub></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><sup>4</sup>''C''<sub>1</sub> &harr; (<sup>4</sup>''H''<sub>3</sub>)<sup>&Dagger;</sup> &harr; <sup>1</sup>''S''<sub>3</sub> &harr; (<sup>4</sup>''H''<sub>3</sub>)<sup>&Dagger;</sup> &harr; <sup>4</sup>''C''<sub>1</sub></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>conformational itinerary. This is the same itinerary employed by [[GH31]] enzymes (also of Clan GH-D, ''vide infra''), while the alpha-<del class="diffchange diffchange-inline">'''L'''</del>-fucosidases of [[GH29]] use the mirror-image itinerary:</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>conformational itinerary. This is the same itinerary employed by [[GH31]] enzymes (also of Clan GH-D, ''vide infra''), while the alpha-<ins class="diffchange diffchange-inline"><u>{{Smallcaps|l}}</u></ins>-fucosidases of [[GH29]] use the mirror-image itinerary:</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><sup>1</sup>''C''<sub>4</sub> &harr; (<sup>3</sup>''H''<sub>4</sub>)<sup>&Dagger;</sup> &harr; <sup>3</sup>''S''<sub>1</sub> &harr; (<sup>3</sup>''H''<sub>4</sub>)<sup>&Dagger;</sup> &harr; <sup>1</sup>''C''<sub>4</sub> (see <cite>LammertsJACS2010</cite> for a full discussion).</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><sup>1</sup>''C''<sub>4</sub> &harr; (<sup>3</sup>''H''<sub>4</sub>)<sup>&Dagger;</sup> &harr; <sup>3</sup>''S''<sub>1</sub> &harr; (<sup>3</sup>''H''<sub>4</sub>)<sup>&Dagger;</sup> &harr; <sup>1</sup>''C''<sub>4</sub> (see <cite>LammertsJACS2010</cite> for a full discussion).</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
</table>Harry Brumerhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_27&diff=4161&oldid=prevHarry Brumer: /* Three-dimensional structures */2010-02-28T09:47:16Z<p><span dir="auto"><span class="autocomment">Three-dimensional structures</span></span></p>
<table class="diff diff-contentalign-left diff-editfont-monospace" data-mw="interface">
<col class="diff-marker" />
<col class="diff-content" />
<col class="diff-marker" />
<col class="diff-content" />
<tr class="diff-title" lang="en-CA">
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">← Older revision</td>
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 09:47, 28 February 2010</td>
</tr><tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l44" >Line 44:</td>
<td colspan="2" class="diff-lineno">Line 44:</td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><sup>4</sup>''C''<sub>1</sub> &harr; (<sup>4</sup>''H''<sub>3</sub>)<sup>&Dagger;</sup> &harr; <sup>1</sup>''S''<sub>3</sub> &harr; (<sup>4</sup>''H''<sub>3</sub>)<sup>&Dagger;</sup> &harr; <sup>4</sup>''C''<sub>1</sub></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><sup>4</sup>''C''<sub>1</sub> &harr; (<sup>4</sup>''H''<sub>3</sub>)<sup>&Dagger;</sup> &harr; <sup>1</sup>''S''<sub>3</sub> &harr; (<sup>4</sup>''H''<sub>3</sub>)<sup>&Dagger;</sup> &harr; <sup>4</sup>''C''<sub>1</sub></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>conformational itinerary. This is the same itinerary employed by [[GH31]] enzymes (also of Clan GH-D, ''vide infra''), while the alpha-'''L'''-fucosidases of [[GH29]] use the mirror-image itinerary:</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>conformational itinerary. This is the same itinerary employed by [[GH31]] enzymes (also of Clan GH-D, ''vide infra''), while the alpha-'''L'''-fucosidases of [[GH29]] use the mirror-image itinerary:</div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><sup>1</sup>''C''<sub>4</sub> &harr; (<sup>3</sup>''H''<sub>4</sub>)<sup>&Dagger;</sup> &harr; <sup>3</sup>''S''<sub>1</sub> &harr; (<sup>3</sup>''H''<sub>4</sub>)<sup>&Dagger;</sup> &harr; <sup>1</sup>''C''<sub>4</sub> <cite>LammertsJACS2010</cite>.</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><sup>1</sup>''C''<sub>4</sub> &harr; (<sup>3</sup>''H''<sub>4</sub>)<sup>&Dagger;</sup> &harr; <sup>3</sup>''S''<sub>1</sub> &harr; (<sup>3</sup>''H''<sub>4</sub>)<sup>&Dagger;</sup> &harr; <sup>1</sup>''C''<sub>4</sub> <ins class="diffchange diffchange-inline">(see </ins><cite>LammertsJACS2010</cite> <ins class="diffchange diffchange-inline">for a full discussion)</ins>.</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>The known overall structures of GH27 enzymes are all highly conserved and the N-terminal domains are all closely superimposable, with minor exceptions including the ''H. jecorina'' (''T. reesei'') alpha-galactosidase <cite>12</cite>, which contains a 40 amino acid insertion in loop beta4-alpha4, and the animal enzymes <cite>3 10</cite>, which contain a short 10 residue insertion in the alpha1-beta1 loop <cite>4</cite>. The C-terminal domains, although similar, are less well conserved, both at the primary and tertiary structural levels <cite>4</cite>. In keeping with the ''[[exo]]'' mode of action of these enzymes, which cleave alpha-Gal from the non-reducing terminii of their substrates, the active sites are pocket-shaped <cite>3 11 12 10</cite>. Specificity for the 2-hydroxyl substituent, in the case of alpha-galactosidases in the family, and the 2-deoxy-2-''N''-acetyl substituent, in the case of the alpha-''N''-acetylgalactosaminidases, is dictated by the presence of correspondingly large or small active-site binding residues, respectively <cite>10</cite> (reviewed in <cite>4</cite>). Based on these observations, phylogenetic analysis has been presented which may have some power to predict specificity within GH27 <cite>10</cite>.</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>The known overall structures of GH27 enzymes are all highly conserved and the N-terminal domains are all closely superimposable, with minor exceptions including the ''H. jecorina'' (''T. reesei'') alpha-galactosidase <cite>12</cite>, which contains a 40 amino acid insertion in loop beta4-alpha4, and the animal enzymes <cite>3 10</cite>, which contain a short 10 residue insertion in the alpha1-beta1 loop <cite>4</cite>. The C-terminal domains, although similar, are less well conserved, both at the primary and tertiary structural levels <cite>4</cite>. In keeping with the ''[[exo]]'' mode of action of these enzymes, which cleave alpha-Gal from the non-reducing terminii of their substrates, the active sites are pocket-shaped <cite>3 11 12 10</cite>. Specificity for the 2-hydroxyl substituent, in the case of alpha-galactosidases in the family, and the 2-deoxy-2-''N''-acetyl substituent, in the case of the alpha-''N''-acetylgalactosaminidases, is dictated by the presence of correspondingly large or small active-site binding residues, respectively <cite>10</cite> (reviewed in <cite>4</cite>). Based on these observations, phylogenetic analysis has been presented which may have some power to predict specificity within GH27 <cite>10</cite>.</div></td></tr>
</table>Harry Brumerhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_27&diff=4160&oldid=prevHarry Brumer at 09:45, 28 February 20102010-02-28T09:45:27Z<p></p>
<table class="diff diff-contentalign-left diff-editfont-monospace" data-mw="interface">
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<tr class="diff-title" lang="en-CA">
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">← Older revision</td>
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 09:45, 28 February 2010</td>
</tr><tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l72" >Line 72:</td>
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<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>#GuceJBC2010 pmid=19940122</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>#GuceJBC2010 pmid=19940122</div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">#LammertsJACS2010 pmid=20092273</ins></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div></biblio></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div></biblio></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><!-- DO NOT REMOVE THIS CATEGORY TAG! --></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><!-- DO NOT REMOVE THIS CATEGORY TAG! --></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Category:Glycoside Hydrolase Families|GH027]]</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Category:Glycoside Hydrolase Families|GH027]]</div></td></tr>
</table>Harry Brumerhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_27&diff=4159&oldid=prevHarry Brumer: /* Three-dimensional structures */2010-02-28T09:44:51Z<p><span dir="auto"><span class="autocomment">Three-dimensional structures</span></span></p>
<table class="diff diff-contentalign-left diff-editfont-monospace" data-mw="interface">
<col class="diff-marker" />
<col class="diff-content" />
<col class="diff-marker" />
<col class="diff-content" />
<tr class="diff-title" lang="en-CA">
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">← Older revision</td>
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 09:44, 28 February 2010</td>
</tr><tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l41" >Line 41:</td>
<td colspan="2" class="diff-lineno">Line 41:</td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Published in 2002, the 3-D structure of the chicken (''Gallus gallus'') ''N''-acetylgalactosaminidase solved by Garman ''et al.'' using X-ray crystallography (1.9 Å resolution) represented the first structure of an enzyme from GH27, and indeed Clan GH-D <cite>3</cite>. Futhermore, the simultaneous solution of an enzyme-product complex (2.4 Å), was instrumental in defining the catalytic acid/base residue in this GH family and clan <cite>3</cite>, as described above. Soon thereafter, structures of the rice (''Oryza sativa'') alpha-galactosidase (2003) <cite>11</cite>, human (''Homo sapiens'') alpha-galactosidase A (2004) <cite>10</cite>, and ''Hypocrea jecorina'' (née ''Trichoderma reesei'') alpha-galactosidase (2004) <cite>12</cite> were presented in both free and product-complexed forms. All of these structures indicated that GH27 enzymes are comprised of an N-terminal (alpha/beta)8 (TIM) barrel domain and a C-terminal anti-parallel beta-jellyroll domain, the former of which contains the enzyme catalytic center composed by loop residues at the ends of beta strands 1-7.</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Published in 2002, the 3-D structure of the chicken (''Gallus gallus'') ''N''-acetylgalactosaminidase solved by Garman ''et al.'' using X-ray crystallography (1.9 Å resolution) represented the first structure of an enzyme from GH27, and indeed Clan GH-D <cite>3</cite>. Futhermore, the simultaneous solution of an enzyme-product complex (2.4 Å), was instrumental in defining the catalytic acid/base residue in this GH family and clan <cite>3</cite>, as described above. Soon thereafter, structures of the rice (''Oryza sativa'') alpha-galactosidase (2003) <cite>11</cite>, human (''Homo sapiens'') alpha-galactosidase A (2004) <cite>10</cite>, and ''Hypocrea jecorina'' (née ''Trichoderma reesei'') alpha-galactosidase (2004) <cite>12</cite> were presented in both free and product-complexed forms. All of these structures indicated that GH27 enzymes are comprised of an N-terminal (alpha/beta)8 (TIM) barrel domain and a C-terminal anti-parallel beta-jellyroll domain, the former of which contains the enzyme catalytic center composed by loop residues at the ends of beta strands 1-7.</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>In 2010, Garman and co-workers published an ensemble of tertiary structures of the human alpha-galactosidase A, which included a trapped covalent 2-deoxy-2,2-difluorogalactosyl-enzyme intermediate in an <sup>1</sup>''S''<sub>3</sub> skew boat conformation <cite>GuceJBC2010</cite>. Together with native, substrate-bound (E&bull;S, Michaelis complex), and product-bound (E&bull;P) structures, this work provided the first complete analysis of substrate distortion along the enzyme reaction coordinate in GH27. Thus, GH27 enzymes use a <sup>4</sup>C<sub>1</sub> &harr; (<sup>4</sup>H<sub>3</sub>)<sup>&Dagger;</sup> &harr; <sup>1</sup>''S''<sub>3</sub> &harr; (<sup>4</sup>H<sub>3</sub>)<sup>&Dagger;</sup> &harr; <sup>4</sup>C<sub>1</sub> conformational itinerary. This is the same itinerary employed by [[GH31]] enzymes (also of Clan GH-D, ''vide infra''), while the alpha-'''L'''-fucosidases of [[GH29]] use the mirror-image itinerary: <sup>1</sup>C<sub>4</sub> &harr; (<sup>3</sup>H<sub>4</sub>)<sup>&Dagger;</sup> &harr; <sup>3</sup>S<sub>1</sub> &harr; (<sup>3</sup>H<sub>4</sub>)<sup>&Dagger;</sup> &harr; <sup>1</sup>C<sub>4</sub> <cite>LammertsJACS2010</cite>.</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>In 2010, Garman and co-workers published an ensemble of tertiary structures of the human alpha-galactosidase A, which included a trapped covalent 2-deoxy-2,2-difluorogalactosyl-enzyme intermediate in an <sup>1</sup>''S''<sub>3</sub> skew boat conformation <cite>GuceJBC2010</cite>. Together with native, substrate-bound (E&bull;S, Michaelis complex), and product-bound (E&bull;P) structures, this work provided the first complete analysis of substrate distortion along the enzyme reaction coordinate in GH27. Thus, GH27 enzymes use a</div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><sup>4</sup><ins class="diffchange diffchange-inline">''</ins>C<ins class="diffchange diffchange-inline">''</ins><sub>1</sub> &harr; (<sup>4</sup><ins class="diffchange diffchange-inline">''</ins>H<ins class="diffchange diffchange-inline">''</ins><sub>3</sub>)<sup>&Dagger;</sup> &harr; <sup>1</sup>''S''<sub>3</sub> &harr; (<sup>4</sup><ins class="diffchange diffchange-inline">''</ins>H<ins class="diffchange diffchange-inline">''</ins><sub>3</sub>)<sup>&Dagger;</sup> &harr; <sup>4</sup><ins class="diffchange diffchange-inline">''</ins>C<ins class="diffchange diffchange-inline">''</ins><sub>1</sub></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>conformational itinerary. This is the same itinerary employed by [[GH31]] enzymes (also of Clan GH-D, ''vide infra''), while the alpha-'''L'''-fucosidases of [[GH29]] use the mirror-image itinerary:</div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><sup>1</sup><ins class="diffchange diffchange-inline">''</ins>C<ins class="diffchange diffchange-inline">''</ins><sub>4</sub> &harr; (<sup>3</sup><ins class="diffchange diffchange-inline">''</ins>H<ins class="diffchange diffchange-inline">''</ins><sub>4</sub>)<sup>&Dagger;</sup> &harr; <sup>3</sup><ins class="diffchange diffchange-inline">''</ins>S<ins class="diffchange diffchange-inline">''</ins><sub>1</sub> &harr; (<sup>3</sup><ins class="diffchange diffchange-inline">''</ins>H<ins class="diffchange diffchange-inline">''</ins><sub>4</sub>)<sup>&Dagger;</sup> &harr; <sup>1</sup><ins class="diffchange diffchange-inline">''</ins>C<ins class="diffchange diffchange-inline">''</ins><sub>4</sub> <cite>LammertsJACS2010</cite>.</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>The known overall structures of GH27 enzymes are all highly conserved and the N-terminal domains are all closely superimposable, with minor exceptions including the ''H. jecorina'' (''T. reesei'') alpha-galactosidase <cite>12</cite>, which contains a 40 amino acid insertion in loop beta4-alpha4, and the animal enzymes <cite>3 10</cite>, which contain a short 10 residue insertion in the alpha1-beta1 loop <cite>4</cite>. The C-terminal domains, although similar, are less well conserved, both at the primary and tertiary structural levels <cite>4</cite>. In keeping with the ''[[exo]]'' mode of action of these enzymes, which cleave alpha-Gal from the non-reducing terminii of their substrates, the active sites are pocket-shaped <cite>3 11 12 10</cite>. Specificity for the 2-hydroxyl substituent, in the case of alpha-galactosidases in the family, and the 2-deoxy-2-''N''-acetyl substituent, in the case of the alpha-''N''-acetylgalactosaminidases, is dictated by the presence of correspondingly large or small active-site binding residues, respectively <cite>10</cite> (reviewed in <cite>4</cite>). Based on these observations, phylogenetic analysis has been presented which may have some power to predict specificity within GH27 <cite>10</cite>.</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>The known overall structures of GH27 enzymes are all highly conserved and the N-terminal domains are all closely superimposable, with minor exceptions including the ''H. jecorina'' (''T. reesei'') alpha-galactosidase <cite>12</cite>, which contains a 40 amino acid insertion in loop beta4-alpha4, and the animal enzymes <cite>3 10</cite>, which contain a short 10 residue insertion in the alpha1-beta1 loop <cite>4</cite>. The C-terminal domains, although similar, are less well conserved, both at the primary and tertiary structural levels <cite>4</cite>. In keeping with the ''[[exo]]'' mode of action of these enzymes, which cleave alpha-Gal from the non-reducing terminii of their substrates, the active sites are pocket-shaped <cite>3 11 12 10</cite>. Specificity for the 2-hydroxyl substituent, in the case of alpha-galactosidases in the family, and the 2-deoxy-2-''N''-acetyl substituent, in the case of the alpha-''N''-acetylgalactosaminidases, is dictated by the presence of correspondingly large or small active-site binding residues, respectively <cite>10</cite> (reviewed in <cite>4</cite>). Based on these observations, phylogenetic analysis has been presented which may have some power to predict specificity within GH27 <cite>10</cite>.</div></td></tr>
</table>Harry Brumerhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_27&diff=4158&oldid=prevHarry Brumer: /* Three-dimensional structures */2010-02-28T09:43:05Z<p><span dir="auto"><span class="autocomment">Three-dimensional structures</span></span></p>
<table class="diff diff-contentalign-left diff-editfont-monospace" data-mw="interface">
<col class="diff-marker" />
<col class="diff-content" />
<col class="diff-marker" />
<col class="diff-content" />
<tr class="diff-title" lang="en-CA">
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">← Older revision</td>
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 09:43, 28 February 2010</td>
</tr><tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l41" >Line 41:</td>
<td colspan="2" class="diff-lineno">Line 41:</td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Published in 2002, the 3-D structure of the chicken (''Gallus gallus'') ''N''-acetylgalactosaminidase solved by Garman ''et al.'' using X-ray crystallography (1.9 Å resolution) represented the first structure of an enzyme from GH27, and indeed Clan GH-D <cite>3</cite>. Futhermore, the simultaneous solution of an enzyme-product complex (2.4 Å), was instrumental in defining the catalytic acid/base residue in this GH family and clan <cite>3</cite>, as described above. Soon thereafter, structures of the rice (''Oryza sativa'') alpha-galactosidase (2003) <cite>11</cite>, human (''Homo sapiens'') alpha-galactosidase A (2004) <cite>10</cite>, and ''Hypocrea jecorina'' (née ''Trichoderma reesei'') alpha-galactosidase (2004) <cite>12</cite> were presented in both free and product-complexed forms. All of these structures indicated that GH27 enzymes are comprised of an N-terminal (alpha/beta)8 (TIM) barrel domain and a C-terminal anti-parallel beta-jellyroll domain, the former of which contains the enzyme catalytic center composed by loop residues at the ends of beta strands 1-7.</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Published in 2002, the 3-D structure of the chicken (''Gallus gallus'') ''N''-acetylgalactosaminidase solved by Garman ''et al.'' using X-ray crystallography (1.9 Å resolution) represented the first structure of an enzyme from GH27, and indeed Clan GH-D <cite>3</cite>. Futhermore, the simultaneous solution of an enzyme-product complex (2.4 Å), was instrumental in defining the catalytic acid/base residue in this GH family and clan <cite>3</cite>, as described above. Soon thereafter, structures of the rice (''Oryza sativa'') alpha-galactosidase (2003) <cite>11</cite>, human (''Homo sapiens'') alpha-galactosidase A (2004) <cite>10</cite>, and ''Hypocrea jecorina'' (née ''Trichoderma reesei'') alpha-galactosidase (2004) <cite>12</cite> were presented in both free and product-complexed forms. All of these structures indicated that GH27 enzymes are comprised of an N-terminal (alpha/beta)8 (TIM) barrel domain and a C-terminal anti-parallel beta-jellyroll domain, the former of which contains the enzyme catalytic center composed by loop residues at the ends of beta strands 1-7.</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>In 2010, Garman and co-workers published an ensemble of tertiary structures of the human alpha-galactosidase A, which included a trapped covalent 2-deoxy-2,2-difluorogalactosyl-enzyme intermediate in an <sup>1</sup>''S''<sub>3</sub> skew boat conformation <cite>GuceJBC2010</cite>. Together with native, substrate-bound (E&bull;S, Michaelis complex), and product-bound (E&bull;P) structures, this work provided the first complete analysis of substrate distortion along the enzyme reaction coordinate in GH27.</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>In 2010, Garman and co-workers published an ensemble of tertiary structures of the human alpha-galactosidase A, which included a trapped covalent 2-deoxy-2,2-difluorogalactosyl-enzyme intermediate in an <sup>1</sup>''S''<sub>3</sub> skew boat conformation <cite>GuceJBC2010</cite>. Together with native, substrate-bound (E&bull;S, Michaelis complex), and product-bound (E&bull;P) structures, this work provided the first complete analysis of substrate distortion along the enzyme reaction coordinate in GH27<ins class="diffchange diffchange-inline">. Thus, GH27 enzymes use a <sup>4</sup>C<sub>1</sub> &harr; (<sup>4</sup>H<sub>3</sub>)<sup>&Dagger;</sup> &harr; <sup>1</sup>''S''<sub>3</sub> &harr; (<sup>4</sup>H<sub>3</sub>)<sup>&Dagger;</sup> &harr; <sup>4</sup>C<sub>1</sub> conformational itinerary. This is the same itinerary employed by [[GH31]] enzymes (also of Clan GH-D, ''vide infra''), while the alpha-'''L'''-fucosidases of [[GH29]] use the mirror-image itinerary: <sup>1</sup>C<sub>4</sub> &harr; (<sup>3</sup>H<sub>4</sub>)<sup>&Dagger;</sup> &harr; <sup>3</sup>S<sub>1</sub> &harr; (<sup>3</sup>H<sub>4</sub>)<sup>&Dagger;</sup> &harr; <sup>1</sup>C<sub>4</sub> <cite>LammertsJACS2010</cite></ins>.</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>The known overall structures of GH27 enzymes are all highly conserved and the N-terminal domains are all closely superimposable, with minor exceptions including the ''H. jecorina'' (''T. reesei'') alpha-galactosidase <cite>12</cite>, which contains a 40 amino acid insertion in loop beta4-alpha4, and the animal enzymes <cite>3 10</cite>, which contain a short 10 residue insertion in the alpha1-beta1 loop <cite>4</cite>. The C-terminal domains, although similar, are less well conserved, both at the primary and tertiary structural levels <cite>4</cite>. In keeping with the ''[[exo]]'' mode of action of these enzymes, which cleave alpha-Gal from the non-reducing terminii of their substrates, the active sites are pocket-shaped <cite>3 11 12 10</cite>. Specificity for the 2-hydroxyl substituent, in the case of alpha-galactosidases in the family, and the 2-deoxy-2-''N''-acetyl substituent, in the case of the alpha-''N''-acetylgalactosaminidases, is dictated by the presence of correspondingly large or small active-site binding residues, respectively <cite>10</cite> (reviewed in <cite>4</cite>). Based on these observations, phylogenetic analysis has been presented which may have some power to predict specificity within GH27 <cite>10</cite>.</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>The known overall structures of GH27 enzymes are all highly conserved and the N-terminal domains are all closely superimposable, with minor exceptions including the ''H. jecorina'' (''T. reesei'') alpha-galactosidase <cite>12</cite>, which contains a 40 amino acid insertion in loop beta4-alpha4, and the animal enzymes <cite>3 10</cite>, which contain a short 10 residue insertion in the alpha1-beta1 loop <cite>4</cite>. The C-terminal domains, although similar, are less well conserved, both at the primary and tertiary structural levels <cite>4</cite>. In keeping with the ''[[exo]]'' mode of action of these enzymes, which cleave alpha-Gal from the non-reducing terminii of their substrates, the active sites are pocket-shaped <cite>3 11 12 10</cite>. Specificity for the 2-hydroxyl substituent, in the case of alpha-galactosidases in the family, and the 2-deoxy-2-''N''-acetyl substituent, in the case of the alpha-''N''-acetylgalactosaminidases, is dictated by the presence of correspondingly large or small active-site binding residues, respectively <cite>10</cite> (reviewed in <cite>4</cite>). Based on these observations, phylogenetic analysis has been presented which may have some power to predict specificity within GH27 <cite>10</cite>.</div></td></tr>
</table>Harry Brumer