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Bacterial chitobiase structure provides insight into catalytic mechanism and the basis of Tay-Sachs disease

Bacterial chitobiase structure provides insight into catalytic mechanism and the basis of Tay-Sachs disease
Bacterial chitobiase structure provides insight into catalytic mechanism and the basis of Tay-Sachs disease
Chitin, the second most abundant polysaccharide on earth, is degraded by chitinases and chitobiases. The structure of Serratia marcescens chitobiase has been refined at 1.9 A resolution. The mature protein is folded into four domains and its active site is situated at the C-terminal end of the central (beta alpha)8-barrel. Based on the structure of the complex with the substrate disaccharide chitobiose, we propose an acid-base reaction mechanism, in which only one protein carboxylate acts as catalytic acid, while the nucleophile is the polar acetamido group of the sugar in a substrate-assisted reaction. The structural data lead to the hypothesis that the reaction proceeds with retention of anomeric configuration. The structure allows us to model the catalytic domain of the homologous hexosaminidases to give a structural rationale to pathogenic mutations that underlie Tay-Sachs and Sandhoff disease.
1072-8368
638-648
Tews, Ivo
9117fc5e-d01c-4f8d-a734-5b14d3eee8dd
Perrakis, A.
c8614d82-a2a7-47bb-980a-3b80139f5866
Oppenheim, A.
e0d161f3-b803-42ea-a2cc-be829da32f47
Dauter, Z.
7c45c437-58e1-4aa6-b451-a18a36c43d2d
Wilson, K. S.
4d607724-1fa3-4f20-a836-382f26cade70
Vorgias, C. E.
3798f345-7b53-49c1-9d27-c7713dac170c
Tews, Ivo
9117fc5e-d01c-4f8d-a734-5b14d3eee8dd
Perrakis, A.
c8614d82-a2a7-47bb-980a-3b80139f5866
Oppenheim, A.
e0d161f3-b803-42ea-a2cc-be829da32f47
Dauter, Z.
7c45c437-58e1-4aa6-b451-a18a36c43d2d
Wilson, K. S.
4d607724-1fa3-4f20-a836-382f26cade70
Vorgias, C. E.
3798f345-7b53-49c1-9d27-c7713dac170c

Tews, Ivo, Perrakis, A., Oppenheim, A., Dauter, Z., Wilson, K. S. and Vorgias, C. E. (1996) Bacterial chitobiase structure provides insight into catalytic mechanism and the basis of Tay-Sachs disease. Nature Structural Biology, 3 (7), 638-648. (PMID:8673609)

Record type: Article

Abstract

Chitin, the second most abundant polysaccharide on earth, is degraded by chitinases and chitobiases. The structure of Serratia marcescens chitobiase has been refined at 1.9 A resolution. The mature protein is folded into four domains and its active site is situated at the C-terminal end of the central (beta alpha)8-barrel. Based on the structure of the complex with the substrate disaccharide chitobiose, we propose an acid-base reaction mechanism, in which only one protein carboxylate acts as catalytic acid, while the nucleophile is the polar acetamido group of the sugar in a substrate-assisted reaction. The structural data lead to the hypothesis that the reaction proceeds with retention of anomeric configuration. The structure allows us to model the catalytic domain of the homologous hexosaminidases to give a structural rationale to pathogenic mutations that underlie Tay-Sachs and Sandhoff disease.

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Published date: July 1996
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 200659
URI: https://eprints.soton.ac.uk/id/eprint/200659
ISSN: 1072-8368
PURE UUID: ff1c374a-6db9-4d1a-a754-c9988dc6f523
ORCID for Ivo Tews: ORCID iD orcid.org/0000-0002-4704-1139

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Date deposited: 02 Nov 2011 14:43
Last modified: 06 Jun 2018 12:33

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