Journal article

Conserved main-chain peptide distortions: A proposed role for Ile203 in catalysis by dihydrodipicolinate synthase

Renwick CJ Dobson, Michael DW Griffin, Sean RA Devenish, F Grant Pearce, Craig A Hutton, Juliet A Gerrard, Geoffrey B Jameson, Matthew A Perugini

PROTEIN SCIENCE | WILEY | Published : 2008

Abstract

In recent years, dihydrodipicolinate synthase (DHDPS, E.C. 4.2.1.52) has received considerable attention from a mechanistic and structural viewpoint. DHDPS catalyzes the reaction of (S)-aspartate-beta-semialdehyde with pyruvate, which is bound via a Schiff base to a conserved active-site lysine (Lys161 in the enzyme from Escherichia coli). To probe the mechanism of DHDPS, we have studied the inhibition of E. coli DHDPS by the substrate analog, beta-hydroxypyruvate. The K (i) was determined to be 0.21 (+/-0.02) mM, similar to that of the allosteric inhibitor, (S)-lysine, and beta-hydroxypyruvate was observed to cause time-dependent inhibition. The inhibitory reaction with beta-hydroxypyruvate..

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Grants

Awarded by Royal Society of New Zealand Marsden


Awarded by Defense Threat Reduction Agency


Awarded by Australian Research Council


Funding Acknowledgements

J.A.G. would like to acknowledge the Royal Society of New Zealand Marsden Fund ( contract UOC303). M. A. P., R. C. J. D., and J. A. G. would like to acknowledge the Defense Threat Reduction Agency ( project W911NF-07-1-0105) and the Australian Research Council (DP0770888). We thank Professor Robert Huber (Max-Planck-Institut fur Biochemie, DE) for supplying the coordinates of the N. sylvestris DHDPS enzyme.