Distortion of a cellobio-derived isofagomine highlights the potential conformational itinerary of inverting β-glucosidases

被引：45

作者：

Varrot, A

Macdonald, J

Stick, RV

Pell, G

Gilbert, HJ

Davies, GJ ^{[1
]}

机构：

[1] Univ York, Dept Chem, Struct Biol Lab, York YO10 5YW, N Yorkshire, England

[2] Univ Western Australia, Sch Biomed & Chem Sci, Crawley, WA 6009, Australia

[3] Univ Newcastle Upon Tyne, Sch Cell & Mol Biosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

来源：

CHEMICAL COMMUNICATIONS | 2003年 / 08期

关键词：

D O I：

10.1039/b301592k

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A cellobio-derived isofagomine glycosidase inhibitor (K-i similar to 400 nM) displays an unusual distorted B-2,B-5 (boat) conformation upon binding to cellobiohydrolase Cel6A from Humicola insolens, highlighting the different conformational itineraries used by various glycosidases, with consequences for the design of therapeutic agents.

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页码：946 / 947

页数：2

相关论文

共 15 条

[1]

DAVIES G, 1997, COMPREHENSIVE BIOL C, V1, P119

[2]

DAVIES GJ, 2003, IN PRESS BIOCH SOC T

[3]

Ducros VMA, 2002, ANGEW CHEM INT EDIT, V41, P2824, DOI 10.1002/1521-3773(20020802)41:15<2824::AID-ANIE2824>3.0.CO

[4]

2-G

[5] Atomic (0.94 Å) resolution structure of an inverting glycosidase in complex with substrate [J].

Guérin, DMA ;

Lascombe, MB ;

Costabel, M ;

Souchon, H ;

Lamzin, V ;

Béguin, P ;

Alzari, PM .

JOURNAL OF MOLECULAR BIOLOGY, 2002, 316 (05) :1061-1069

[6] The active site of cellobiohydrolase Cel6A from Trichoderma reesei:: The roles of aspartic acids D221 and D175 [J].

Koivula, A ;

Ruohonen, L ;

Wohlfahrt, G ;

Reinikainen, T ;

Teeri, TT ;

Piens, K ;

Claeyssens, M ;

Weber, M ;

Vasella, A ;

Becker, D ;

Sinnott, ML ;

Zou, JY ;

Kleywegt, GJ ;

Szardenings, M ;

Ståhlberg, J ;

Jones, TA .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2002, 124 (34) :10015-10024

[7] Synthesis with glycosynthases: Cello-oligomers of isofagomine and a tetrahydrooxazine as cellulase inhibitors [J].

Macdonald, JM ;

Stick, RV ;

Tilbrook, DMG ;

Withers, SG .

AUSTRALIAN JOURNAL OF CHEMISTRY, 2002, 55 (12) :747-752

[8] Mechanism of Agrobacterium beta-glucosidase: Kinetic analysis of the role of noncovalent enzyme/substrate interactions [J].

Namchuk, MN ;

Withers, SG .

BIOCHEMISTRY, 1995, 34 (49) :16194-16202

[9] Catalysis and specificity in enzymatic glycoside hydrolysis:: a 2,5B conformation for the glycosyl-enzyme intermediate revealed by the structure of the Bacillus agaradhaerens family 11 xylanase [J].

Sabini, E ;

Sulzenbacher, G ;

Dauter, M ;

Dauter, Z ;

Jorgensen, PL ;

Schülein, M ;

Dupont, C ;

Davies, GJ ;

Wilson, KS .

CHEMISTRY & BIOLOGY, 1999, 6 (07) :483-492

[10]

Stoddart J. F., 1971, STEREOCHEMISTRY CARB