1E5J

ENDOGLUCANASE CEL5A FROM BACILLUS AGARADHAERENS IN THE TETRAGONAL CRYSTAL FORM IN COMPLEX WITH METHYL-4II-S-ALPHA-CELLOBIOSYL-4II-THIO-BETA-CELLOBIOSIDE

Summary for 1E5J

• Entry DOI: 10.2210/pdb1e5j/pdb
• Related: 1QHZ 1QI0 1QI2 4A3H 8A3H
• Descriptor: ENDOGLUCANASE 5A, alpha-D-glucopyranose-(1-4)-4-thio-beta-D-glucopyranose-(1-4)-4-thio-beta-D-glucopyranose-(1-4)-methyl beta-D-glucopyranoside, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: hydrolase, cellulose degradation, glycoshydrolase family 5
• Biological source: BACILLUS AGARADHAERENS
• Total number of polymer chains: 1
• Total formula weight: 35029.23

Authors

Fort, S.,Varrot, A.,Schulein, M.,Cottaz, S.,Driguez, H.,Davies, G.J. (deposition date: 2000-07-26, release date: 2001-07-26, Last modification date: 2024-05-08)

Primary citation

Fort, S.,Varrot, A.,Schulein, M.,Cottaz, S.,Driguez, H.,Davies, G.J.
Mixed-Linkage Cellooligosaccharides: A New Class of Glycoside Hydrolase Inhibitors
Chembiochem, 2:319-, 2001

PubMed Abstract: 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.

PubMed: 11828460
DOI: 10.1002/1439-7633(20010504)2:5<319::AID-CBIC319>3.3.CO;2-H

Experimental method

X-RAY DIFFRACTION (1.85 Å)