Structural and mechanistic basis for a new mode of glycosyltransferase inhibition

Thomas Pesnot; Rene Jørgensen; Monica M. Palcic; Gerd K. Wagner

doi:10.1038/nchembio.343

Structural and mechanistic basis for a new mode of glycosyltransferase inhibition

Thomas Pesnot, Rene Jørgensen, Monica M. Palcic, Gerd K. Wagner

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Abstract

Glycosyltransferases are carbohydrate-active enzymes with essential roles in numerous important biological processes. We have developed a new donor analog for galactosyltransferases that locks a representative target enzyme in a catalytically inactive conformation, thus almost completely abolishing sugar transfer. Results with other galactosyltransferases suggest that this unique mode of glycosyltransferase inhibition may also be generally applicable to other members of this important enzyme family.

Originalsprog	Engelsk
Tidsskrift	Nature Chemical Biology
Vol/bind	6
Udgave nummer	5
Sider (fra-til)	321-323
Antal sider	3
ISSN	1552-4450
DOI	https://doi.org/10.1038/nchembio.343
Status	Udgivet - maj 2010
Udgivet eksternt	Ja

Bibliografisk note

Funding Information:
We thank D.D. Djurhuus, D. Adlercreutz and M.H. Bien for excellent technical assistance during this research. The plasmid for the Neisseria meningitidis α-1,4-GalT was a generous gift from W.W. Wakarchuk (National Research Council of Canada). AA(Gly)B was cloned by H.J. Lee (University of Alberta) and N.O.L. Seto (National Research Council of Canada). We also thank A. Henriksen (Carlsberg Laboratory) for supplying equipment and tools for protein crystallography and for helpful discussions. We are grateful for the help with X-ray data collection provided by the beamline staff at I-911 at MAX-lab (Lund, Sweden) and at X12 at Deutsches Elektronen-Synchrotron (European Molecular Biology Laboratory, Hamburg, Germany). This work was supported by the UK Engineering and Physical Sciences Research Council (First Grant EP/D059186/1 to G.K.W.), the UK Medical Research Council (Discipline Hopping Award G0701861 to G.K.W.), the Leverhulme Trust (Research Fellowship RF/4/RFG/2008/0544 to G.K.W.) and the Danish Agency for Science, Technology and Innovation (grant 272-08-0449 to M.M.P.). We thank the Engineering and Physical Sciences Research Council National Mass Spectrometry Service Centre, Swansea, for the recording of mass spectra.

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10.1038/nchembio.343

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