The Chitopentaose Complex of a Mutant Hen Egg-White Lysozyme Displays No Distortion of the-1 Sugar Away from a C-4(1) Chair Conformation

Gideon J. Davies; Stephen G. Withers; David J. Vocadlo

doi:10.1071/CH09038

The Chitopentaose Complex of a Mutant Hen Egg-White Lysozyme Displays No Distortion of the-1 Sugar Away from a C-4(1) Chair Conformation

Gideon J. Davies, Stephen G. Withers, David J. Vocadlo

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

Glycosidase inhibitors frequently reflect either the charge or the 'flattened' shape of the oxocarbenium-ion like transition state. Much of the impetus for such inhibitory strategies derives from historical studies on ligand binding to hen egg white lysozyme (HEWL); not least those suggesting that product complexes of the enzyme showed distortion of the pyranosides in the -1 subsite. Ironically, while distortion is undoubtedly a defining feature of glycosidases, product complexes themselves are rarely distorted. Here we show that the chitopentaose product complex of a mutant E35Q HEWL, solved at 1.8 angstrom resolution, is bound with all sugars in C-4(1) conformation.

Original language	English
Pages (from-to)	528-532
Number of pages	5
Journal	Australian Journal of Chemistry
Volume	62
Issue number	6
DOIs	https://doi.org/10.1071/CH09038
Publication status	Published - 2009

Keywords

X-RAY CRYSTALLOGRAPHY
BETA-GLUCOSIDASES
CRYSTAL-STRUCTURE
TRANSITION-STATE
SITE-D
BINDING
CATALYSIS
ISOFAGOMINE
INHIBITORS
MECHANISMS

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10.1071/CH09038

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title = "The Chitopentaose Complex of a Mutant Hen Egg-White Lysozyme Displays No Distortion of the-1 Sugar Away from a C-4(1) Chair Conformation",

abstract = "Glycosidase inhibitors frequently reflect either the charge or the 'flattened' shape of the oxocarbenium-ion like transition state. Much of the impetus for such inhibitory strategies derives from historical studies on ligand binding to hen egg white lysozyme (HEWL); not least those suggesting that product complexes of the enzyme showed distortion of the pyranosides in the -1 subsite. Ironically, while distortion is undoubtedly a defining feature of glycosidases, product complexes themselves are rarely distorted. Here we show that the chitopentaose product complex of a mutant E35Q HEWL, solved at 1.8 angstrom resolution, is bound with all sugars in C-4(1) conformation.",

keywords = "X-RAY CRYSTALLOGRAPHY, BETA-GLUCOSIDASES, CRYSTAL-STRUCTURE, TRANSITION-STATE, SITE-D, BINDING, CATALYSIS, ISOFAGOMINE, INHIBITORS, MECHANISMS",

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journal = "Australian Journal of Chemistry",

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AU - Vocadlo, David J.

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N2 - Glycosidase inhibitors frequently reflect either the charge or the 'flattened' shape of the oxocarbenium-ion like transition state. Much of the impetus for such inhibitory strategies derives from historical studies on ligand binding to hen egg white lysozyme (HEWL); not least those suggesting that product complexes of the enzyme showed distortion of the pyranosides in the -1 subsite. Ironically, while distortion is undoubtedly a defining feature of glycosidases, product complexes themselves are rarely distorted. Here we show that the chitopentaose product complex of a mutant E35Q HEWL, solved at 1.8 angstrom resolution, is bound with all sugars in C-4(1) conformation.

AB - Glycosidase inhibitors frequently reflect either the charge or the 'flattened' shape of the oxocarbenium-ion like transition state. Much of the impetus for such inhibitory strategies derives from historical studies on ligand binding to hen egg white lysozyme (HEWL); not least those suggesting that product complexes of the enzyme showed distortion of the pyranosides in the -1 subsite. Ironically, while distortion is undoubtedly a defining feature of glycosidases, product complexes themselves are rarely distorted. Here we show that the chitopentaose product complex of a mutant E35Q HEWL, solved at 1.8 angstrom resolution, is bound with all sugars in C-4(1) conformation.

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KW - CRYSTAL-STRUCTURE

KW - TRANSITION-STATE

KW - SITE-D

KW - BINDING

KW - CATALYSIS

KW - ISOFAGOMINE

KW - INHIBITORS

KW - MECHANISMS

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JO - Australian Journal of Chemistry

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IS - 6

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The Chitopentaose Complex of a Mutant Hen Egg-White Lysozyme Displays No Distortion of the-1 Sugar Away from a C-4(1) Chair Conformation

Abstract

Keywords

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