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

Nature Structural Biology volume 3, pages 638–648 (1996)Cite this 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 Å resolution. The mature protein is folded into four domains and its active site is situated at the C-terminal end of the central (βα)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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Authors and Affiliations

  1. European Molecular Biology Laboratory, Hamburg Outstation Notkestraße 85, 22603, Hamburg, Germany

    Ivo Tews, Anastassis Perrakis, Zbigniew Dauter & Keith S. Wilson

  2. Department of Molecular Genetics The Hebrew University-Hadassah Medical School, Jerusalem, 90101, Israel

    Amos Oppenheim

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  1. From September 1996 C.E.V will move to: Athens University, Biology Department, Biochemistry Laboratory, Panepistimiopoli, Kouponia, 15701 Athens, Greece

    • Constantin E. Vorgias
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Tews, I., Perrakis, A., Oppenheim, A. et al. Bacterial chitobiase structure provides insight into catalytic mechanism and the basis of Tay–Sachs disease. Nat Struct Mol Biol 3, 638–648 (1996). https://doi.org/10.1038/nsb0796-638

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