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Difference between revisions of "Glycoside Hydrolase Family 6"
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== Three-dimensional structures == | == Three-dimensional structures == | ||
| − | + | The first crystal structures of cellobiohydrolases and endoglucanases from family GH7 revealed modified a/b barrel folds which, unlike the classical (b/a)<sub>8</sub> "TIM" barrel has just seven b-strands forming the central b-barrel. The CBHII structure revealed an active centre (see above) enclosed in a tunnel formed primarily by two surface loops. When, subsequently, the first endoglucanase from this family was solved the active center was observed in a long open groove. The comparison of these two structures thus provided the first insight into how endo or processive activity was modulated, through display of the active centre in a in an open grove, or loop-enclosed tunnel, respectively. | |
| + | The nature of how catalysis was achived, and the conformational itinerary of catalysis was first provided by the Uppsala, Grenoble and Gent groups in 1999 was a trapped Michaelis complex of a thio oligosaccharide was observed spanninbg the avtive centre with the -1 subsite sugar in <sup>2</sup>S<sub>O</sub> conformation. | ||
== Family Firsts == | == Family Firsts == | ||
Revision as of 07:05, 4 October 2010
This page is currently under construction. This means that the Responsible Curator has deemed that the page's content is not quite up to CAZypedia's standards for full public consumption. All information should be considered to be under revision and may be subject to major changes.
- Author: ^^^Kathleen Piens^^^ and ^^^Gideon Davies^^^
- Responsible Curator: ^^^Gideon Davies^^^
| Glycoside Hydrolase Family GH6 | |
| Clan | none |
| Mechanism | inverting |
| Active site residues | acid known, base debated |
| CAZy DB link | |
| http://www.cazy.org/fam/GH6.html | |
Substrate specificities
Glycoside hydrolases of family 6 cleave β-1,4 glycosidic bonds in cellulose/β-1,4-glucans. Only endoglucanase (EC 3.2.1.4) and cellobiohydrolase (EC 3.2.1.91) activity has been reported for both bacterial and eukaryotic members of this family.
Kinetics and Mechanism
Family 6 enzymes are inverting enzymes, as first shown by NMR [1] on Cellobiohydrolase II (CBH II; Cel6A) from the fungus Trichoderma reesei (a clonal derivative of Hypocrea jecorina [2]).
Catalytic Residues
Content is to be added here.
| Proposed role | CfCel6A (endo) | HiCel6A (exo) | HjCel6A (exo) | TfCel6A (endo) | TfCel6B (exo) |
|---|---|---|---|---|---|
| Substrate distortion | Tyr210 | Tyr174 | Tyr169 | Tyr73 | Tyr220 |
| Increase in pKa acid/Catalytic base | Asp216 | Asp180 | Asp175 | Asp79 | Asp226 |
| Proton network | Gly222? | Ser186 | Ser181 | Ser85 | Ser232 |
| Catalytic acid | Asp252 | Asp226 | Asp221 | Asp117 | Asp274 |
| Catalytic base/substrate binding | Asp392 | Asp405 | Asp401 | Asp265 | Asp497 |
Three-dimensional structures
The first crystal structures of cellobiohydrolases and endoglucanases from family GH7 revealed modified a/b barrel folds which, unlike the classical (b/a)8 "TIM" barrel has just seven b-strands forming the central b-barrel. The CBHII structure revealed an active centre (see above) enclosed in a tunnel formed primarily by two surface loops. When, subsequently, the first endoglucanase from this family was solved the active center was observed in a long open groove. The comparison of these two structures thus provided the first insight into how endo or processive activity was modulated, through display of the active centre in a in an open grove, or loop-enclosed tunnel, respectively. The nature of how catalysis was achived, and the conformational itinerary of catalysis was first provided by the Uppsala, Grenoble and Gent groups in 1999 was a trapped Michaelis complex of a thio oligosaccharide was observed spanninbg the avtive centre with the -1 subsite sugar in 2SO conformation.
Family Firsts
- First sterochemistry determination
- Hypocrea jecorina cellobiohydrolase Cel6A by NMR [1].
- First general acid/base residue identification
- Cite some reference here, with a short (1-2 senetence) explanation.
- First 3-D structure
- The catalytic core domain of the Trichoderma reesei (the organism now known as Hypocrea jecorina) cellobiohydrolase II by the Jones group [3]. The first endoglucanase in this family was the Thermomonospora fusca E2 enzyme (catalytic core) solved by the Wilson/Karplus groups[4]
References
-
Knowles, J.K.C., Lehtovaara, P., Murray, M. and Sinnott, M.L. (1988) Stereochemical course of the action of the cellobioside hydrolases I and II of Trichoderma reesei. J. Chem. Soc., Chem. Commun., 1988, 1401-1402. DOI: 10.1039/C39880001401
- Kuhls K, Lieckfeldt E, Samuels GJ, Kovacs W, Meyer W, Petrini O, Gams W, Börner T, and Kubicek CP. (1996). Molecular evidence that the asexual industrial fungus Trichoderma reesei is a clonal derivative of the ascomycete Hypocrea jecorina. Proc Natl Acad Sci U S A. 1996;93(15):7755-60. DOI:10.1073/pnas.93.15.7755 |
- Rouvinen J, Bergfors T, Teeri T, Knowles JK, and Jones TA. (1990). Three-dimensional structure of cellobiohydrolase II from Trichoderma reesei. Science. 1990;249(4967):380-6. DOI:10.1126/science.2377893 |
- Spezio M, Wilson DB, and Karplus PA. (1993). Crystal structure of the catalytic domain of a thermophilic endocellulase. Biochemistry. 1993;32(38):9906-16. DOI:10.1021/bi00089a006 |