Journal article

The high-resolution structure of dihydrodipicolinate synthase from Escherichia coli bound to its first substrate, pyruvate

Sean RA Devenish, Juliet A Gerrard, Geoffrey B Jameson, Renwick CJ Dobson

ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS | INT UNION CRYSTALLOGRAPHY | Published : 2008

Abstract

Dihydrodipicolinate synthase (DHDPS) mediates the key first reaction common to the biosynthesis of (S)-lysine and meso-diaminopimelate, molecules which play a crucial cross-linking role in bacterial cell walls. An effective inhibitor of DHDPS would represent a useful antibacterial agent; despite extensive effort, a suitable inhibitor has yet to be found. In an attempt to examine the specificity of the active site of DHDPS, the enzyme was cocrystallized with the substrate analogue oxaloacetate. The resulting crystals diffracted to 2.0 A resolution, but solution of the protein structure revealed that pyruvate was bound in the active site rather than oxaloacetic acid. Kinetic analysis confirmed..

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Grants

Awarded by Royal Society of New Zealand Marsden


Funding Acknowledgements

SRAD is grateful for funding from the Foundation for Research Science and Technology. Further funding was provided by the Royal Society of New Zealand Marsden fund (contract UOC303). Funding for the protein X-ray diffraction facility was provided in part by The Allan Wilson Centre for Molecular Ecology and Evolution. The authors wish to acknowledge Jackie Healy (University of Canterbury, New Zealand) for unswerving technical assistance.