Glycoside Hydrolase Family 136 - Revision history

Harry Brumer at 19:57, 25 June 2023

2023-06-25T19:57:29Z

Harry Brumer: /* Three-dimensional structures */

2023-06-25T19:51:45Z

Three-dimensional structures

Harry Brumer: fixed PDB links

2023-06-25T19:50:53Z

fixed PDB links

Harry Brumer: added PDB links

2023-06-25T19:49:58Z

added PDB links

Harry Brumer: fixed broken Yamada reference

2023-06-25T19:44:04Z

fixed broken Yamada reference

Shinya Fushinobu at 08:06, 23 June 2023

2023-06-23T08:06:58Z

Shinya Fushinobu: Mechanism and family firsts

2023-06-16T02:45:48Z

Mechanism and family firsts

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

2021-12-18T21:15:56Z

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

Chihaya Yamada at 01:02, 4 March 2021

2021-03-04T01:02:44Z

Chihaya Yamada at 08:26, 3 March 2021

2021-03-03T08:26:34Z

@@ Line 28: / Line 28: @@
 == Substrate specificities ==
-This family of glycoside hydrolases contains lacto-''N''-biosidase, as demonstrated for LnbX from ''Bifidobacterium longum'' JCM 1217 <cite>Sakurama2013</cite>. LnbX liberates Galβ1-3GlcNAc (lacto-''N''-biose I, LNB) and lactose from lacto-''N''-tetraose, the main component of human milk oligosaccharides. It hydrolyzed the linkage GlcNAcβ1-3Gal in lacto-''N''-hexaose, lacto-''N''-fucopentaose I, and sialyllacto-''N''-tetraose a of human milk oligosaccharides as substrate of LnbX in the GH136. In addition, LnbX liberates Galβ1-3GalNAc (GNB) from the sugar chains of globo- and ganglio-series glycosphingolipids <cite>Gotoh2015</cite>.
+This family of glycoside hydrolases contains lacto-''N''-biosidase, as demonstrated for LnbX from ''Bifidobacterium longum'' JCM 1217 <cite>Sakurama2013</cite>. LnbX liberated Galβ1-3GlcNAc (lacto-''N''-biose I, LNB) and lactose from lacto-''N''-tetraose, the main component of human milk oligosaccharides. It hydrolyzed the linkage GlcNAcβ1-3Gal in lacto-''N''-hexaose, lacto-''N''-fucopentaose I, and sialyllacto-''N''-tetraose a of human milk oligosaccharides as substrate of LnbX in the GH136. In addition, LnbX liberated Galβ1-3GalNAc (GNB) from the sugar chains of globo- and ganglio-series glycosphingolipids <cite>Gotoh2015</cite>.
-Majority of GH136 lacto-''N''-biosidases require a neighboring chaperon gene for folding. Rarely, chaperone-like gene is fused to lacto-''N''-biosidase gene in case of ErLnb136<sub>I</sub> and ErLnb136<sub>II</sub> from ''Eubacterium ramulus'' <cite>Michael2020</cite>.
+The majority of GH136 lacto-''N''-biosidases require a neighboring chaperone gene for folding. Rarely, the chaperone-like gene is fused to the lacto-''N''-biosidase gene, as in case of ErLnb136<sub>I</sub> and ErLnb136<sub>II</sub> from ''Eubacterium ramulus'' <cite>Michael2020</cite>.
 == Kinetics and Mechanism ==
-GH136 lacto-''N''-biosidases hydrolyze the glycosidic linkage via anomer-retaining mechanism. The acid/base catalytic residue of LnbX (Asp411) formed a water-mediated hydrogen bond with the O1 atom of GlcNAc at subsite -1, and a mechanism of Grotthuss proton transfer was proposed <cite>chihaya2017</cite>. However, subsequent crystallographic reports on three GH136 lacto-''N''-biosidases ("Er"Lnb136, BsaX, and TnX) revealed a direct hydrogen bond between the acid/base catalyst and the O1 atom. This observation suggests that a direct proton transfer mechanism is prevalent within this family <cite>Michael2020 Yamada2022</cite>.
+GH136 lacto-''N''-biosidases hydrolyze the glycosidic linkage via a anomer-[[retaining]] mechanism. The [[general acid/base]] catalytic residue of LnbX (Asp411) formed a water-mediated hydrogen bond with the O1 atom of GlcNAc at subsite -1, and a mechanism of Grotthuss proton transfer was proposed <cite>chihaya2017</cite>. However, subsequent crystallographic reports on three GH136 lacto-''N''-biosidases ("Er"Lnb136, BsaX, and TnX) revealed a direct hydrogen bond between the [[general acid/base]] catalyst and the O1 atom. This observation suggests that a direct proton transfer mechanism is prevalent within this family <cite>Michael2020 Yamada2022</cite>.
 == Catalytic Residues ==
-For LnbX, the nucleophile and the catalytic acid/base are Asp418 and Asp411, respectively.
+For LnbX, the [[catalytic nucleophile]] and the catalytic [[general acid/base]] are Asp418 and Asp411, respectively.
 == Three-dimensional structures ==

@@ Line 42: / Line 42: @@
 [[file:ErGH136.png|thumb|300px|right|'''Figure 2: '''Overall structure of ''Er''Lnb136 with LNB (yellow), consisting of an N-terminal domain designated as ''Er''Lnb136<sub>I</sub> (cyan-blue) and a C-terminal β-helix domain (green) -''Er''Lnb136<sub>II</sub>.]]
-The X-ray crystal structure of the catalytic domain, LnbXc(31-625) revealed a right-handed β helix fold that is usually shared by polysaccharide-active enzymes. Three forms, ligand free at 2.36 Å resolution (PDB ID [{{PDBlink}}5GQC 5GQC]), LNB complex at 1.82 Å (PDB ID [{{PDBlink}}5GQF 5GQF]), and GNB complex at 2.70 Å (PDB ID [{{PDBlink}}5GQG 5GQG) were determined <cite>chihaya2017</cite>.
+The X-ray crystal structure of the catalytic domain, LnbXc(31-625) revealed a right-handed β helix fold that is usually shared by polysaccharide-active enzymes. Three forms, ligand free at 2.36 Å resolution (PDB ID [{{PDBlink}}5GQC 5GQC]), LNB complex at 1.82 Å (PDB ID [{{PDBlink}}5GQF 5GQF]), and GNB complex at 2.70 Å (PDB ID [{{PDBlink}}5GQG 5GQG]) were determined <cite>chihaya2017</cite>.
-The X-ray crystal structure of '' Er''GH136 in complex with LNB (PDB ID 6KQT) revealed the N-terminal domain (''Er''Lnb136I, from AA 7-224) consists of 8 α-helices (α1-α8) and Y145 of the α6-α7 loop positioned near the active site <cite>Michael2020</cite>. The LNB-complexed structures of the catalytic domain of BsaX from ''Bifidobacterium saguini'' and TnX from ''Tyzzerella nexilis'' were also reported <cite>Yamada2022</cite>.
+The X-ray crystal structure of '' Er''GH136 in complex with LNB (PDB ID [{{PDBlink}}6KQT 6KQT]) revealed the N-terminal domain (''Er''Lnb136I, from AA 7-224) consists of 8 α-helices (α1-α8) and Y145 of the α6-α7 loop positioned near the active site <cite>Michael2020</cite>. The LNB-complexed structures of the catalytic domain of BsaX from ''Bifidobacterium saguini'' and TnX from ''Tyzzerella nexilis'' were also reported <cite>Yamada2022</cite>.
 == Family Firsts ==

@@ Line 42: / Line 42: @@
 [[file:ErGH136.png|thumb|300px|right|'''Figure 2: '''Overall structure of ''Er''Lnb136 with LNB (yellow), consisting of an N-terminal domain designated as ''Er''Lnb136<sub>I</sub> (cyan-blue) and a C-terminal β-helix domain (green) -''Er''Lnb136<sub>II</sub>.]]
-The X-ray crystal structure of the catalytic domain, LnbXc(31-625) revealed a right-handed β helix fold that is usually shared by polysaccharide-active enzymes. Three forms, ligand free at 2.36 Å resolution (PDB ID [{{PBDlink}}5GQC 5GQC]), LNB complex at 1.82 Å (PDB ID [{{PBDlink}}5GQF 5GQF]), and GNB complex at 2.70 Å (PDB ID [{{PBDlink}}5GQG 5GQG) were determined <cite>chihaya2017</cite>.
+The X-ray crystal structure of the catalytic domain, LnbXc(31-625) revealed a right-handed β helix fold that is usually shared by polysaccharide-active enzymes. Three forms, ligand free at 2.36 Å resolution (PDB ID [{{PDBlink}}5GQC 5GQC]), LNB complex at 1.82 Å (PDB ID [{{PDBlink}}5GQF 5GQF]), and GNB complex at 2.70 Å (PDB ID [{{PDBlink}}5GQG 5GQG) were determined <cite>chihaya2017</cite>.
 The X-ray crystal structure of '' Er''GH136 in complex with LNB (PDB ID 6KQT) revealed the N-terminal domain (''Er''Lnb136I, from AA 7-224) consists of 8 α-helices (α1-α8) and Y145 of the α6-α7 loop positioned near the active site <cite>Michael2020</cite>. The LNB-complexed structures of the catalytic domain of BsaX from ''Bifidobacterium saguini'' and TnX from ''Tyzzerella nexilis'' were also reported <cite>Yamada2022</cite>.

@@ Line 42: / Line 42: @@
 [[file:ErGH136.png|thumb|300px|right|'''Figure 2: '''Overall structure of ''Er''Lnb136 with LNB (yellow), consisting of an N-terminal domain designated as ''Er''Lnb136<sub>I</sub> (cyan-blue) and a C-terminal β-helix domain (green) -''Er''Lnb136<sub>II</sub>.]]
-The X-ray crystal structure of the catalytic domain, LnbXc(31-625) revealed a right-handed β helix fold that is usually shared by polysaccharide-active enzymes. Three forms, ligand free at 2.36 Å resolution (PDB ID 5GQC), LNB complex at 1.82 Å (PDB ID 5GQF), and GNB complex at 2.70 Å (PDB ID 5GQG) were determined <cite>chihaya2017</cite>.
+The X-ray crystal structure of the catalytic domain, LnbXc(31-625) revealed a right-handed β helix fold that is usually shared by polysaccharide-active enzymes. Three forms, ligand free at 2.36 Å resolution (PDB ID [{{PBDlink}}5GQC 5GQC]), LNB complex at 1.82 Å (PDB ID [{{PBDlink}}5GQF 5GQF]), and GNB complex at 2.70 Å (PDB ID [{{PBDlink}}5GQG 5GQG) were determined <cite>chihaya2017</cite>.
 The X-ray crystal structure of '' Er''GH136 in complex with LNB (PDB ID 6KQT) revealed the N-terminal domain (''Er''Lnb136I, from AA 7-224) consists of 8 α-helices (α1-α8) and Y145 of the α6-α7 loop positioned near the active site <cite>Michael2020</cite>. The LNB-complexed structures of the catalytic domain of BsaX from ''Bifidobacterium saguini'' and TnX from ''Tyzzerella nexilis'' were also reported <cite>Yamada2022</cite>.

@@ Line 57: / Line 57: @@
 #chihaya2017 pmid=28392148
 #Michael2020 pmid=32620774
-#Yamada2020 pmid=35092420
+#Yamada2022 pmid=35092420
 </biblio>
 [[Category:Glycoside Hydrolase Families|GH136]]

@@ Line 1: / Line 1: @@
-<!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption -->
+{{CuratorApproved}}
 * [[Author]]: [[User:Chihaya Yamada|Chihaya Yamada]]
 * [[Responsible Curator]]:  [[User:Shinya Fushinobu|Shinya Fushinobu]]

@@ Line 29: / Line 29: @@
 == Substrate specificities ==
-This family of glycoside hydrolases contains lacto-''N''-biosidase, as demonstrated for LnbX from ''Bifidobacterium longum'' JCM 1217 <cite>Sakurama2013</cite>. LnbX liberates Galβ1-3GlcNAc(lacto-''N''-biose I, LNB) and lactose from lacto-''N''-tetraose, the main component of human milk oligosaccharides. It hydrolyzed the linkage GlcNAcβ1-3Gal in lacto-''N''-hexaose, lacto-''N''-fucopentaose I, and sialyllacto-''N''-tetraose a of human milk oligosaccharides as substrate of LnbX in the GH136. In addition, LnbX liberates Galβ1-3GalNAc (GNB) from the sugar chains of globo- and ganglio-series glycosphingolipids <cite>Gotoh2015</cite>.
+This family of glycoside hydrolases contains lacto-''N''-biosidase, as demonstrated for LnbX from ''Bifidobacterium longum'' JCM 1217 <cite>Sakurama2013</cite>. LnbX liberates Galβ1-3GlcNAc (lacto-''N''-biose I, LNB) and lactose from lacto-''N''-tetraose, the main component of human milk oligosaccharides. It hydrolyzed the linkage GlcNAcβ1-3Gal in lacto-''N''-hexaose, lacto-''N''-fucopentaose I, and sialyllacto-''N''-tetraose a of human milk oligosaccharides as substrate of LnbX in the GH136. In addition, LnbX liberates Galβ1-3GalNAc (GNB) from the sugar chains of globo- and ganglio-series glycosphingolipids <cite>Gotoh2015</cite>.
 == Kinetics and Mechanism ==
-LnbX hydrolyzes the glycosidic linkage via a retaining mechanism involving a Grotthuss proton relay.
+GH136 lacto-''N''-biosidases hydrolyze the glycosidic linkage via anomer-retaining mechanism. The acid/base catalytic residue of LnbX (Asp411) formed a water-mediated hydrogen bond with the O1 atom of GlcNAc at subsite -1, and a mechanism of Grotthuss proton transfer was proposed <cite>chihaya2017</cite>. However, subsequent crystallographic reports on three GH136 lacto-''N''-biosidases ("Er"Lnb136, BsaX, and TnX) revealed a direct hydrogen bond between the acid/base catalyst and the O1 atom. This observation suggests that a direct proton transfer mechanism is prevalent within this family <cite>Michael2020 Yamada2022</cite>.
 == Catalytic Residues ==
-The nucleophile is Asp418. The catalytic acid/base is Asp411 via water molecule.
+For LnbX, the nucleophile and the catalytic acid/base are Asp418 and Asp411, respectively.
 == Three-dimensional structures ==
@@ Line 44: / Line 43: @@
 [[file:ErGH136.png|thumb|300px|right|'''Figure 2: '''Overall structure of ''Er''Lnb136 with LNB (yellow), consisting of an N-terminal domain designated as ''Er''Lnb136<sub>I</sub> (cyan-blue) and a C-terminal β-helix domain (green) -''Er''Lnb136<sub>II</sub>.]]
-The X-ray crystal structure of the catalytic domain, LnbXc(31-625) revealed a right-handed β helix fold that is usually shared by polysaccharide active enzymes. Three forms, ligand free at 2.36 Å resolution (PDB ID 5GQC), LNB complex at 1.82 Å (PDB ID 5GQF), and GNB complex at 2.70 Å (PDB ID 5GQG) were determined <cite>chihaya2017</cite>.
+The X-ray crystal structure of the catalytic domain, LnbXc(31-625) revealed a right-handed β helix fold that is usually shared by polysaccharide-active enzymes. Three forms, ligand free at 2.36 Å resolution (PDB ID 5GQC), LNB complex at 1.82 Å (PDB ID 5GQF), and GNB complex at 2.70 Å (PDB ID 5GQG) were determined <cite>chihaya2017</cite>.
-The X-ray crystal structure of'' Er''GH136 in complex with LNB (PDB ID 6KQT) revealed the N-terminal domain (''Er''Lnb136I, from AA 7-224) consists of 8 α-helices (α1-α8)　and Y145 of the α6-α7 loop positioned near the active site <cite>Michael2020</cite>.
+The X-ray crystal structure of '' Er''GH136 in complex with LNB (PDB ID 6KQT) revealed the N-terminal domain (''Er''Lnb136I, from AA 7-224) consists of 8 α-helices (α1-α8) and Y145 of the α6-α7 loop positioned near the active site <cite>Michael2020</cite>. The LNB-complexed structures of the catalytic domain of BsaX from ''Bifidobacterium saguini'' and TnX from ''Tyzzerella nexilis'' were also reported <cite>Yamada2022</cite>.
 == Family Firsts ==
-;First stereochemistry determination: Content is to be added here.
+;First stereochemistry determination: LnbX from ''Bifidobacterium longum'' <cite>Sakurama2013</cite>.
-;First catalytic nucleophile identification: Content is to be added here.
+;First catalytic nucleophile identification: LnbX from ''Bifidobacterium longum'' <cite>chihaya2017</cite>.
-;First general acid/base residue identification: Content is to be added here.
+;First general acid/base residue identification: LnbX from ''Bifidobacterium longum'' <cite>chihaya2017</cite>.
-;First 3-D structure: Content is to be added here.
+;First 3-D structure: LnbX from ''Bifidobacterium longum'' <cite>chihaya2017</cite>.
 == References ==
@@ Line 59: / Line 58: @@
 #chihaya2017 pmid=28392148
 #Michael2020 pmid=32620774
 </biblio>
 [[Category:Glycoside Hydrolase Families|GH136]]