The Chitopentaose Complex of a Mutant Hen Egg-White Lysozyme Displays No Distortion of the –1 Sugar Away from a 4C1 Chair Conformation

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

doi:10.1071/CH09038

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The Chitopentaose Complex of a Mutant Hen Egg-White Lysozyme Displays No Distortion of the –1 Sugar Away from a ⁴C₁ Chair Conformation

Gideon J. Davies ^A ^D , Stephen G. Withers ^B and David J. Vocadlo ^C

+ Author Affiliations

- Author Affiliations

^A Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York, UK.

^B Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, B.C., V6T 1Z1, Canada.

^C Department of Chemistry, Simon Fraser University, 8888 University Drive, Burnaby, Canada.

^D Corresponding author. Email: davies@ysbl.york.ac.uk

Australian Journal of Chemistry 62(6) 528-532 https://doi.org/10.1071/CH09038
Submitted: 17 January 2009 Accepted: 13 February 2009 Published: 10 June 2009

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 Å resolution, is bound with all sugars in ⁴C₁ conformation.

Acknowledgements

The authors thank Roger Laine for the provision of the E35Q HEWL protein (see reference [29]). The Peter Wall Institute for Advanced Studies (University of British Columbia) is thanked for the provision of a ‘catalytic visitor’ award to G.J.D. to facilitate this work. We thank the Natural Sciences and Engineering Research Council and the Protein Engineering Network of Centres of Excellence of Canada for funding. G.J.D. is currently a Royal Society-Wolfson Research Merit Award recipient. D.J.V. is currently a Scholar of the Michael Smith Foundation for Health Research and the Canada Research Chair in Chemical Glycobiology. The Natalie Strynadka group (University of British Columbia) are thanked for their generous provision of X-ray and computing time to aid this work.

References

The Chitopentaose Complex of a Mutant Hen Egg-White Lysozyme Displays No Distortion of the –1 Sugar Away from a 4C1 Chair Conformation

Abstract

Acknowledgements

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The Chitopentaose Complex of a Mutant Hen Egg-White Lysozyme Displays No Distortion of the –1 Sugar Away from a ⁴C₁ Chair Conformation