1e5j
From Proteopedia
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ENDOGLUCANASE CEL5A FROM BACILLUS AGARADHAERENS IN THE TETRAGONAL CRYSTAL FORM IN COMPLEX WITH METHYL-4II-S-ALPHA-CELLOBIOSYL-4II-THIO BETA-CELLOBIOSIDE
Overview
A new class of inhibitors for beta-D-glycoside hydrolases, in which a, single alpha-(1-->4)-glycosidic bond is incorporated into an otherwise, all-beta-(1-->4)-linked oligosaccharide, is described. Such mixed, beta/alpha-linkage cellooligosaccharides are not transition-state mimics, but instead are capable of utilising binding energy from numerous, subsites, spanning either side of the catalytic centre, without the need, for substrate distortion. This binding is significant; a mixed, alpha/beta-D-tetrasaccharide acts competitively on a number of cellulases, displaying inhibition constants in the range of 40-300 microM. Using the, Bacillus agaradhaerens enzyme Cel5A as a model system, one such mixed, beta/alpha-cellooligosaccharide, methyl, 4(II),4(III)-dithio-alpha-cellobiosyl-(1-->4)-beta-cellobioside, displays, a K(i) value of 100 microM, an inhibition at least 150 times better than, is observed with an equivalent all-beta-linked compound. The, three-dimensional structure of B. agaradhaerens Cel5A in complex with, methyl 4(II),4(III)-dithio-alpha-cellobiosyl-(1-->4)-beta-cellobioside has, been determined at 1.8 A resolution. This confirms the expected mode of, binding in which the ligand, with all four pyranosides in the (4)C(1), chair conformation, occupies the -3, -2 and +1 subsites whilst evading the, catalytic (-1) subsite. Such "by-pass" compounds offer great scope for the, development of a new class of beta-D-glycoside hydrolase inhibitors.
About this Structure
1E5J is a Single protein structure of sequence from Bacillus agaradhaerens with GLC, SGC and CA as ligands. Active as Cellulase, with EC number 3.2.1.4 Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Mixed-linkage cellooligosaccharides: a new class of glycoside hydrolase inhibitors., Fort S, Varrot A, Schulein M, Cottaz S, Driguez H, Davies GJ, Chembiochem. 2001 May 4;2(5):319-25. PMID:11828460
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