Glycoside Hydrolase Family 146 - Revision history

Harry Brumer: Text replacement - "\^\^\^(.*)\^\^\^" to "$1"

2021-12-18T21:20:16Z

Text replacement - "\^\^\^(.*)\^\^\^" to "$1"

Kazune Tamura at 16:02, 20 March 2020

2020-03-20T16:02:22Z

Spencer Williams: /* Family Firsts */

2018-02-16T21:39:10Z

Family Firsts

Spencer Williams at 21:38, 16 February 2018

2018-02-16T21:38:40Z

Harry Gilbert at 18:26, 15 February 2018

2018-02-15T18:26:34Z

Harry Gilbert at 18:24, 15 February 2018

2018-02-15T18:24:56Z

Harry Gilbert at 18:23, 15 February 2018

2018-02-15T18:23:33Z

Harry Gilbert at 17:39, 15 February 2018

2018-02-15T17:39:50Z

Harry Gilbert at 17:38, 15 February 2018

2018-02-15T17:38:56Z

Harry Gilbert at 17:37, 15 February 2018

2018-02-15T17:37:52Z

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 <!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption -->
 {{CuratorApproved}}
-* [[Author]]: ^^^Jonathon Briggs^^^
+* [[Author]]: [[User:Jonathon Briggs|Jonathon Briggs]]
-* [[Responsible Curator]]:  ^^^Harry Gilbert^^^
+* [[Responsible Curator]]:  [[User:Harry Gilbert|Harry Gilbert]]
 ----

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 == Three-dimensional structures ==
-[[File:BT0349newnew.png|thumb|300px|right|'''Figure 1.'''  The 3D crystal structure of BT0349 showing the N-terminal (α/α)<sub>5</sub> barrel catalytic domain in green and the three &beta;-sandwich domains in cyan, magenta and yellow from the N- to the C-terminus ([{{PDBlink}}5OPJ PDB ID 5OPJ]). The arabinose bound in the active site is shown in red and the catalytic resisdues are in blue slate. The zinc in the active is  in grey.]]The crystal structure of BT0349, solved using single-wavelength anomalous dispersion methods to a resolution of 2.1 A, revealed a four-domain structure. The N-terminal catalytic domain comprises an (α/α)<sub>5</sub> barrel followed by three β-sandwich domains (1, 2 & 3). Arabinofuranose was present in the active site pocket of the catalytic domain, while a zinc atom is coordinated by three cysteine residues and a glutamate in the same domain <cite>Luis2018</cite>. The catalytic apparatus is conserved with a [[GH127]] β-arabinofuranosidase <cite>Ito2014</cite>; however, the GH127 enzyme lacks β-sandwich domain 3, which is positioned over the active site, effectively burying the bound arabinofuranose. GH127 enzymes were shown to cleave glycosidic bonds with retention of anomeric configuration <cite>Fujita2014</cite> and, given the conservation of the catalytic apparatus in GH127 and GH146 members, enzymes in both families were proposed to hydrolyse arabinofururanosidic bonds through a retaining mechanism <cite>Luis2018</cite>.
+[[File:BT0349newnew.png|thumb|300px|right|'''Figure 1.'''  The 3D crystal structure of BT0349 showing the N-terminal (α/α)<sub>6</sub> barrel catalytic domain in green and the three &beta;-sandwich domains in cyan, magenta and yellow from the N- to the C-terminus ([{{PDBlink}}5OPJ PDB ID 5OPJ]). The arabinose bound in the active site is shown in red and the catalytic resisdues are in blue slate. The zinc in the active is  in grey.]]The crystal structure of BT0349, solved using single-wavelength anomalous dispersion methods to a resolution of 2.1 A, revealed a four-domain structure. The N-terminal catalytic domain comprises an (α/α)<sub>6</sub> barrel followed by three β-sandwich domains (1, 2 & 3). Arabinofuranose was present in the active site pocket of the catalytic domain, while a zinc atom is coordinated by three cysteine residues and a glutamate in the same domain <cite>Luis2018</cite>. The catalytic apparatus is conserved with a [[GH127]] β-arabinofuranosidase <cite>Ito2014</cite>; however, the GH127 enzyme lacks β-sandwich domain 3, which is positioned over the active site, effectively burying the bound arabinofuranose. GH127 enzymes were shown to cleave glycosidic bonds with retention of anomeric configuration <cite>Fujita2014</cite> and, given the conservation of the catalytic apparatus in GH127 and GH146 members, enzymes in both families were proposed to hydrolyse arabinofururanosidic bonds through a retaining mechanism <cite>Luis2018</cite>.
 == Family Firsts ==
 ;First stereochemistry determination: Retaining mechanism of the ''B. thetaiotaomicron''  β-arabinofuranosidase, BT0349 <cite>Luis2018</cite>, based on conservation of the catalytic apparatus with retaining GH127 enzymes <cite>Fujita2014,Ito2014</cite>.
 ;First catalytic nucleophile identification: Cys414 of the ''B. thetaiotaomicron''  β-arabinofuranosidase, BT0349, based on mutagenesis data, 3D structure <cite>Luis2018</cite> and conservation with the catalytic nucleophile of GH127 enzymes <cite>Ito2014</cite>.
 ;First general acid/base residue identification: Glu318 of the ''B. thetaiotaomicron''  β-arabinofuranosidase, BT0349, based on mutagenesis data, 3D structure  <cite>Luis2018</cite>and conservation with the catalytic nucleophile of GH127 enzymes <cite>Ito2014</cite>.
-;First 3-D structure: The ''B. thetaiotaomicron''  β-arabinofuranosidase, BT0349. The enzyme contains an N-terminal catalytic domain that folds into a (α/α)<sub>5</sub> barrel, which is followed by three β-sandwich domains.
+;First 3-D structure: The ''B. thetaiotaomicron''  β-arabinofuranosidase, BT0349. The enzyme contains an N-terminal catalytic domain that folds into a (α/α)<sub>6</sub> barrel, which is followed by three β-sandwich domains.
 == References ==

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 ;First catalytic nucleophile identification: Cys414 of the ''B. thetaiotaomicron''  β-arabinofuranosidase, BT0349, based on mutagenesis data, 3D structure <cite>Luis2018</cite> and conservation with the catalytic nucleophile of GH127 enzymes <cite>Ito2014</cite>.
 ;First general acid/base residue identification: Glu318 of the ''B. thetaiotaomicron''  β-arabinofuranosidase, BT0349, based on mutagenesis data, 3D structure  <cite>Luis2018</cite>and conservation with the catalytic nucleophile of GH127 enzymes <cite>Ito2014</cite>.
-;First 3-D structure: The ''B. thetaiotaomicron''  β-arabinofuranosidase, BT0349. The enzyme contains an N-terminal catalytic domain that folds into a (α/α)<sub>5</sub> barrel, which is followed by three β-sandwich domains
+;First 3-D structure: The ''B. thetaiotaomicron''  β-arabinofuranosidase, BT0349. The enzyme contains an N-terminal catalytic domain that folds into a (α/α)<sub>5</sub> barrel, which is followed by three β-sandwich domains.
 == References ==

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 == Substrate specificities ==
-This glycoside hydrolase family has only one assigned activity to date, β-arabinofuranosidase. The founding member of this family, BT0349 from ''Bacteroides thetaiotaomicron'', was shown to cleave both β1,2- and β1,3-linked arabinofuranose side chains present in branched sugar beet arabinan <cite>Luis2018</cite>.
+Enzymes of this family of [[glycoside hydrolases]] exhibit β-arabinofuranosidase activity. The founding member of this family, BT0349 from ''Bacteroides thetaiotaomicron'', cleaves both β1,2- and β1,3-linked arabinofuranose side chains present in branched sugar beet arabinan <cite>Luis2018</cite>.
 == Kinetics and Mechanism ==
-The only characterised GH146 enzyme, the ''B. thetaiotaomicron''  β-arabinofuranosidase BT0349, displays exo-activity on β-linked arabinofuranose by deploying a retaining mechanism, based on the positions of the catalytic residues (see below) <cite>Luis2018</cite>.
+BT0349 β-arabinofuranosidase displays ''[[exo]]''-activity on β-linked arabinofuranosyl groups and has been proposed to act with a [[retaining]] mechanism, based on the positions of the catalytic residues (see below) <cite>Luis2018</cite>.
 == Catalytic Residues ==
-The catalytic nucleophile and general acid/base residues of the founding member of GH146, BT0349, were proposed to comprise Cys414 and Glu318, respectively <cite>Luis2018</cite>. This is based on the conservation of these residues with the catalytic apparatus of GH127 β-arabinofuranosidases <cite>Ito2014</cite>.
+The catalytic nucleophile and general acid/base residues of BT0349 are proposed to comprise Cys414 and Glu318, respectively <cite>Luis2018</cite>. This is based on the conservation of these residues with the catalytic apparatus of [[GH127]] β-arabinofuranosidases <cite>Ito2014</cite>.
 == Three-dimensional structures ==
-[[File:BT0349newnew.png|thumb|300px|right|'''Figure 1.'''  The 3D crystal structure of BT0349 showing the N-terminal (α/α)<sub>5</sub> barrel catalytic domain in green and the three &beta;-sandwich domains in cyan, magenta and yellow from the N- to the C-terminus ([{{PDBlink}}5OPJ PDB ID 5OPJ]). The arabinose bound in the active site is shown in red and the catalytic resisdues are in blue slate. The zinc in the active is  in grey.]]The crystal structure of BT0349, solved using SAD methods to a resolution of 2.1 A, revealed a four-domain structure. The N-terminal catalytic domain comprises an (α/α)<sub>5</sub> barrel followed by three β-sandwich domains (1, 2 & 3). An arabinofuranose is present in the active site pocket of the catalytic domain, while a zinc atom is coordinated by three cysteine residues and a glutamate in the same domain <cite>Luis2018</cite>. The catalytic apparatus is completely conserved with a GH127 β-arabinofuranosidase <cite>Ito2014</cite>ref, however, the GH127 enzyme lacks β-sandwich domain 3, which is positioned over the active site, effectively burying the bound arabinofuranose. GH127 enzymes were shown to cleave glycosidic bonds with retention of anomeric configuration <cite>Fujita2014</cite> and, given the conservation of the catalytic apparatus in GH127 and GH146 members, enzymes in both families were proposed to hydrolyse arabinofururanosidic bonds through a retaining mechanism <cite>Luis2018</cite>.
+[[File:BT0349newnew.png|thumb|300px|right|'''Figure 1.'''  The 3D crystal structure of BT0349 showing the N-terminal (α/α)<sub>5</sub> barrel catalytic domain in green and the three &beta;-sandwich domains in cyan, magenta and yellow from the N- to the C-terminus ([{{PDBlink}}5OPJ PDB ID 5OPJ]). The arabinose bound in the active site is shown in red and the catalytic resisdues are in blue slate. The zinc in the active is  in grey.]]The crystal structure of BT0349, solved using single-wavelength anomalous dispersion methods to a resolution of 2.1 A, revealed a four-domain structure. The N-terminal catalytic domain comprises an (α/α)<sub>5</sub> barrel followed by three β-sandwich domains (1, 2 & 3). Arabinofuranose was present in the active site pocket of the catalytic domain, while a zinc atom is coordinated by three cysteine residues and a glutamate in the same domain <cite>Luis2018</cite>. The catalytic apparatus is conserved with a [[GH127]] β-arabinofuranosidase <cite>Ito2014</cite>; however, the GH127 enzyme lacks β-sandwich domain 3, which is positioned over the active site, effectively burying the bound arabinofuranose. GH127 enzymes were shown to cleave glycosidic bonds with retention of anomeric configuration <cite>Fujita2014</cite> and, given the conservation of the catalytic apparatus in GH127 and GH146 members, enzymes in both families were proposed to hydrolyse arabinofururanosidic bonds through a retaining mechanism <cite>Luis2018</cite>.
 == Family Firsts ==
 ;First stereochemistry determination: Retaining mechanism of the ''B. thetaiotaomicron''  β-arabinofuranosidase, BT0349 <cite>Luis2018</cite>, based on conservation of the catalytic apparatus with retaining GH127 enzymes <cite>Fujita2014,Ito2014</cite>.
 ;First catalytic nucleophile identification: Cys414 of the ''B. thetaiotaomicron''  β-arabinofuranosidase, BT0349, based on mutagenesis data, 3D structure <cite>Luis2018</cite> and conservation with the catalytic nucleophile of GH127 enzymes <cite>Ito2014</cite>.
 ;First general acid/base residue identification: Glu318 of the ''B. thetaiotaomicron''  β-arabinofuranosidase, BT0349, based on mutagenesis data, 3D structure  <cite>Luis2018</cite>and conservation with the catalytic nucleophile of GH127 enzymes <cite>Ito2014</cite>.
 ;First 3-D structure: The ''B. thetaiotaomicron''  β-arabinofuranosidase, BT0349. The enzyme contains an N-terminal catalytic domain that folds into a (α/α)<sub>5</sub> barrel, which is followed by three β-sandwich domains

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 <!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption -->
-{{UnderConstruction}}
+{{CuratorApproved}}
 * [[Author]]: ^^^Jonathon Briggs^^^
 * [[Responsible Curator]]:  ^^^Harry Gilbert^^^

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 == References ==
 <biblio>
-#Luis2017 pmid=29255254
+#Luis2018 pmid=29255254
 #Ito2014 pmid=24680821

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 #Ito2014 pmid=24680821
-#Fujita2014 pmid=
+#Fujita2014 pmid=24385433
 </biblio>
 [[Category:Glycoside Hydrolase Families|GH146]]