1ocq

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Template:STRUCTURE 1ocq

COMPLEX OF THE ENDOGLUCANASE CEL5A FROM BACILLUS AGARADHEARANS AT 1.08 ANGSTROM RESOLUTION WITH CELLOBIO-DERIVED ISOFAGOMINE


Overview

Glycosidases are some of the most ubiquitous enzyme in nature. Their biological significance, coupled to their enormous catalytic prowess derived from tight binding of the transition state, is reflected in their importance as therapeutic targets. Many glycosidase inhibitors are known. Imino sugars are often potent inhibitors, yet many facets of their mode of action, such as their degree, if any, of transition-state "mimicry" and their protonation state when bound to the target glycosidase remain unclear. Atomic resolution analysis of the endoglucanase, Cel5A, in complex with a cellobio-derived isofagomine in conjunction with the pH dependence of Ki and kcat/KM reveals that this compound binds as a protonated sugar. Surprisingly, both the enzymatic nucleophile and the acid/base are unprotonated in the complex.

About this Structure

1OCQ is a Single protein structure of sequence from Bacillus agaradhaerens. Full crystallographic information is available from OCA.

Reference

Direct observation of the protonation state of an imino sugar glycosidase inhibitor upon binding., Varrot A, Tarling CA, Macdonald JM, Stick RV, Zechel DL, Withers SG, Davies GJ, J Am Chem Soc. 2003 Jun 25;125(25):7496-7. PMID:12812472 Page seeded by OCA on Sat May 3 03:40:26 2008

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