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Difference between revisions of "Glycoside Hydrolase Family 98"
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| − | {{ | + | * [[Author]]: [[User:Fathima Shaikh|Fathima Shaikh]] |
| − | * [[Author]]: | + | * [[Responsible Curator]]: [[User:Al Boraston|Al Boraston]] |
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{| {{Prettytable}} | {| {{Prettytable}} | ||
|- | |- | ||
| − | |{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family | + | |{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH98''' |
|- | |- | ||
|'''Clan''' | |'''Clan''' | ||
| − | | | + | |Not assigned |
|- | |- | ||
|'''Mechanism''' | |'''Mechanism''' | ||
| Line 22: | Line 21: | ||
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link''' | |{{Hl2}} colspan="2" align="center" |'''CAZy DB link''' | ||
|- | |- | ||
| − | | colspan="2" | | + | | colspan="2" |{{CAZyDBlink}}GH98.html |
|} | |} | ||
</div> | </div> | ||
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== Substrate specificities == | == Substrate specificities == | ||
| − | The glycoside | + | The [[glycoside hydrolase]]s of this family are [[endo]]-β-galactosidases. No other activities have been reported. Family 98 glycoside hydrolases are unique in their specificity towards cleavage of the type II core [gal(β1-4)glcNAc] in the AB blood group antigens (EABase, Sp3GH98) and Lewis<sup>Y</sup> antigens (SpGH98) <cite>Ashida2005 Higgins2009 Shaikh2009</cite>. These enzymes are capable of processing these glycans when presented on cell surfaces thus destroying the antigens <cite>Ashida2005 Higgins2009</cite>. |
== Kinetics and Mechanism == | == Kinetics and Mechanism == | ||
| − | + | Family GH98 galactosidases are [[inverting]] enzymes, as first shown by NMR monitoring of the Sp4GH98-catalyzed hydrolysis of the Lewis<sup>Y</sup> tetrasaccharide <cite>Higgins2009</cite>. EABase was also shown to act through an inverting enzyme by NMR monitoring of the EABase catalysed hydrolysis of an artificial substrate, DNP-A-trisaccharide <cite>Shaikh2009</cite>. These results are contrary to the initial predictions made by Rigden <cite>Rigden2005</cite>. EABase follows normal Michaelis-Menten kinetics <cite>Shaikh2009</cite>. | |
| − | Family GH98 galactosidases are inverting enzymes, as first shown by NMR monitoring of the Sp4GH98 catalyzed hydrolysis of the | ||
| − | |||
== Catalytic Residues == | == Catalytic Residues == | ||
| − | + | The [[general base]], an aspartate and glutamate diad, and the [[general acid]], glutamate, were identified through the crystal structures of Sp3GH98 and Sp4GH98 in complex with the A trisaccharide and H disaccharide, respectively, and confirmed by site-directed mutagenesis <cite>Higgins2009</cite>. Similar results were obtained through kinetic studies of the corresponding acid and base mutants of EABase with the artificial substrate dinitrophenyl A-trisaccharide. Further biochemical evidence for the catalytic acid residue was obtained by comparison between the activity of the acid mutant and the p''K''<sub>a</sub> of the leaving group of the substrate <cite>Shaikh2009</cite>. | |
| − | The | ||
== Three-dimensional structures == | == Three-dimensional structures == | ||
| − | + | The first crystal structures from family 98 were the Sp3GH98 and Sp4GH98 enzymes from ''S. pneumoniae'' in complex with the A trisaccharide and H disaccharide respectively <cite>Higgins2009</cite>. Both structures feature a (α/β)<sub>8</sub> barrel in the catalytic domain with an adjoining β-sandwich domain that contributes to the architecture of the active site and helps define the respective specificities of the enzymes <cite>Higgins2009</cite> | |
| − | The first crystal structures from family 98 were the Sp3GH98 and Sp4GH98 enzymes from ''S. pneumoniae'' in complex with the A trisaccharide and H disaccharide respectively <cite>Higgins2009</cite>. Both structures feature a (α/β)<sub> 8</sub> barrel in the catalytic domain <cite>Higgins2009</cite> | ||
| − | |||
== Family Firsts == | == Family Firsts == | ||
| + | ;First sterochemistry determination | ||
| + | :''Streptococcus pneumoniae'' TIGR4 endo-beta-galactosidase Sp4GH98 by NMR <cite>Higgins2009</cite>. | ||
| + | ;First [[general base]] identification | ||
| + | :''Streptococcus pneumoniae'' SP3-BS71 endo-beta-galactosidase Sp3GH98 <cite>Higgins2009</cite>. | ||
| + | :''Streptococcus pneumoniae'' TIGR4 endo-beta-galactosidase Sp4GH98 <cite>Higgins2009</cite>. | ||
| − | ;First | + | ;First [[general acid]] identification |
| − | ''Streptococcus pneumoniae'' | + | :''Streptococcus pneumoniae'' SP3-BS71 endo-beta-galactosidase Sp3GH98 <cite>Higgins2009</cite>. |
| − | + | :''Streptococcus pneumoniae'' TIGR4 endo-beta-galactosidase Sp4GH98 <cite>Higgins2009</cite>. | |
| − | |||
| − | |||
| − | |||
| − | |||
| − | |||
| − | |||
| − | Streptococcus pneumoniae TIGR4 endo-beta-galactosidase Sp4GH98 <cite>Higgins2009</cite>. | ||
| − | ;First 3-D | + | ;First 3-D structures |
| − | Streptococcus pneumoniae SP3-BS71 endo-beta-galactosidase Sp3GH98 <cite>Higgins2009</cite>. | + | :''Streptococcus pneumoniae'' SP3-BS71 endo-beta-galactosidase Sp3GH98 <cite>Higgins2009</cite>. |
| − | Streptococcus pneumoniae TIGR4 endo-beta-galactosidase Sp4GH98 <cite>Higgins2009</cite>. | + | :''Streptococcus pneumoniae'' TIGR4 endo-beta-galactosidase Sp4GH98 <cite>Higgins2009</cite>. |
== References == | == References == | ||
Latest revision as of 13:20, 18 December 2021
This page has been approved by the Responsible Curator as essentially complete. CAZypedia is a living document, so further improvement of this page is still possible. If you would like to suggest an addition or correction, please contact the page's Responsible Curator directly by e-mail.
| Glycoside Hydrolase Family GH98 | |
| Clan | Not assigned |
| Mechanism | Inverting |
| Active site residues | Known |
| CAZy DB link | |
| https://www.cazy.org/GH98.html | |
Substrate specificities
The glycoside hydrolases of this family are endo-β-galactosidases. No other activities have been reported. Family 98 glycoside hydrolases are unique in their specificity towards cleavage of the type II core [gal(β1-4)glcNAc] in the AB blood group antigens (EABase, Sp3GH98) and LewisY antigens (SpGH98) [1, 2, 3]. These enzymes are capable of processing these glycans when presented on cell surfaces thus destroying the antigens [1, 2].
Kinetics and Mechanism
Family GH98 galactosidases are inverting enzymes, as first shown by NMR monitoring of the Sp4GH98-catalyzed hydrolysis of the LewisY tetrasaccharide [2]. EABase was also shown to act through an inverting enzyme by NMR monitoring of the EABase catalysed hydrolysis of an artificial substrate, DNP-A-trisaccharide [3]. These results are contrary to the initial predictions made by Rigden [4]. EABase follows normal Michaelis-Menten kinetics [3].
Catalytic Residues
The general base, an aspartate and glutamate diad, and the general acid, glutamate, were identified through the crystal structures of Sp3GH98 and Sp4GH98 in complex with the A trisaccharide and H disaccharide, respectively, and confirmed by site-directed mutagenesis [2]. Similar results were obtained through kinetic studies of the corresponding acid and base mutants of EABase with the artificial substrate dinitrophenyl A-trisaccharide. Further biochemical evidence for the catalytic acid residue was obtained by comparison between the activity of the acid mutant and the pKa of the leaving group of the substrate [3].
Three-dimensional structures
The first crystal structures from family 98 were the Sp3GH98 and Sp4GH98 enzymes from S. pneumoniae in complex with the A trisaccharide and H disaccharide respectively [2]. Both structures feature a (α/β)8 barrel in the catalytic domain with an adjoining β-sandwich domain that contributes to the architecture of the active site and helps define the respective specificities of the enzymes [2]
Family Firsts
- First sterochemistry determination
- Streptococcus pneumoniae TIGR4 endo-beta-galactosidase Sp4GH98 by NMR [2].
- First general base identification
- Streptococcus pneumoniae SP3-BS71 endo-beta-galactosidase Sp3GH98 [2].
- Streptococcus pneumoniae TIGR4 endo-beta-galactosidase Sp4GH98 [2].
- First general acid identification
- Streptococcus pneumoniae SP3-BS71 endo-beta-galactosidase Sp3GH98 [2].
- Streptococcus pneumoniae TIGR4 endo-beta-galactosidase Sp4GH98 [2].
- First 3-D structures
- Streptococcus pneumoniae SP3-BS71 endo-beta-galactosidase Sp3GH98 [2].
- Streptococcus pneumoniae TIGR4 endo-beta-galactosidase Sp4GH98 [2].
References
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