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Glycoside Hydrolase Family 8
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|Glycoside Hydrolase Family 8|
|Active site residues||known|
|CAZy DB link|
Glycoside hydrolases of family 8 cleave β-1,4 linkages of β-1,4 glucans, xylans (or xylooligosaccharides), chitosans, and lichenans (1,3-1,4-β-D-glucan). All of GH8 members have been found from bacteria, and there are no members from Eukaryotic or Archaeal origin. The majority of the enzymes are endo-acting enzymes, but one member has an exo-activity that releases β-D-xylose residues from the reducing end of xylooligosaccharides. The substrate specificities found in GH8 are: chitosanase (EC 126.96.36.199), cellulase (EC 188.8.131.52), licheninase (EC 184.108.40.206), endo-1,4-β-xylanase (EC 220.127.116.11) and reducing-end-xylose releasing exo-oligoxylanase (EC 18.104.22.168). GH8 was one of the first glycoside hydrolase families classified by hydrophobic cluster analysis, and was previously known as "Cellulase Family D" [1, 2].
Kinetics and Mechanism
Enzymes of glycoside hydrolase family 8 are inverting enzymes, as first shown by Fierobe et al. who monitored the reaction of endoglucanase C from Clostridium cellulolyticum (CelCCC) using proton NMR spectroscopy . Hydrolysis by CelA was computationally simulated with QM/MM metadynamics .
Reducing-end-xylose releasing exo-oligoxylanase from Bacillus halodurans C-125 is the first inverting GH that was converted to glycosynthase by mutating the general base residue .
The general acid (proton donor to the leaving group) was first identified in CelA from C. thermocellum as Glu95 . The general base (proton acceptor from the nucleophilic water) of GH8a subfamily was first identified in CelA from C. thermocellum as Asp278 . The general base of GH8b subfamily was first identified in chitosanase from Bacillus sp. K17 as Glu309 based on its crystal structure and by making E309Q mutant .
Several three-dimensional structures of GH8 members from bacterial origin have been solved. The first solved 3-D structure was endoglucanase CelA from Clostridium thermocellum (PDB ID 1cem) in 1996 . As members of Clan GH-M they have a (α/α)6 fold similar to Glycoside Hydrolase Family 48. The general acid residue is located at the N-terminal end of α4 helix. Position of the general base differ among #Subfamilies. Atomic (0.94 Å) resolution structure of CelA in complex with substrate (PDB ID 1kwf) has been determined .
GH8 enzymes are divided into at least three subfamilies, depending on the position of the general base . GH8a has the general base (Asp) at the N-terminal end of α8 helix. GH8a contains cellulases, xylanases and other enzymes. In GH8b enzymes, the Asp residue is replaced by Asn, and the general base is a Glu residue located in a long loop inserted between α7 and α8 helices. GH8b contains chitosanases, licheninases, cellulases and other enzymes. The position of the general base in GH8c is unknown.
- First sequence identification
- Cellulase (celA) from Clostridium thermocellum 
- First sterochemistry determination
- Endoglucanase C from Clostridium cellulolyticum (CelCCC) 
- First general acid residue identification
- Cellulase (CelA) from Clostridium thermocellum 
- First general base residue identification of GH8a
- Cellulase (CelA) from Clostridium thermocellum 
- First general base residue identification of GH8b
- Chitosanase from Bacillus sp. K17 by crystal structure and a mutant .
- First 3-D structure
- Endoglucanase CelA from Clostridium thermocellum by X-ray crystallography (PDB ID 1cem) .
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- Henrissat B, Claeyssens M, Tomme P, Lemesle L, and Mornon JP. (1989). Cellulase families revealed by hydrophobic cluster analysis. Gene. 1989;81(1):83-95. DOI:10.1016/0378-1119(89)90339-9 |
- Gilkes NR, Henrissat B, Kilburn DG, Miller RC Jr, and Warren RA. (1991). Domains in microbial beta-1, 4-glycanases: sequence conservation, function, and enzyme families. Microbiol Rev. 1991;55(2):303-15. DOI:10.1128/mr.55.2.303-315.1991 |
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- Guérin DM, Lascombe MB, Costabel M, Souchon H, Lamzin V, Béguin P, and Alzari PM. (2002). Atomic (0.94 A) resolution structure of an inverting glycosidase in complex with substrate. J Mol Biol. 2002;316(5):1061-9. DOI:10.1006/jmbi.2001.5404 |
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