Structure and evolution of a novel dimeric enzyme from a clinically important bacterial pathogen

BR Burgess; RCJ Dobson; MF Bailey; SC Atkinson; MDW Griffin; GB Jameson; MW Parker; JA Gerrard; MA Perugini

Journal article

Structure and evolution of a novel dimeric enzyme from a clinically important bacterial pathogen

BR Burgess, RCJ Dobson, MF Bailey, SC Atkinson, MDW Griffin, GB Jameson, MW Parker, JA Gerrard, MA Perugini

Journal of Biological Chemistry | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2008

DOI: 10.1074/jbc.M804231200

Abstract

Dihydrodipicolinate synthase (DHDPS) catalyzes the first committed step of the lysine biosynthetic pathway. The tetrameric structure of DHDPS is thought to be essential for enzymatic activity, as isolated dimeric mutants of Escherichia coli DHDPS possess less than 2.5% that of the activity of the wildtype tetramer. It has recently been proposed that the dimeric form lacks activity due to increased dynamics. Tetramerization, by buttressing two dimers together, reduces dynamics in the dimeric unit and explains why all active bacterial DHDPS enzymes to date have been shown to be homo-tetrameric. However, in this study we demonstrate for the first time that DHDPS from methicillin-resistant Staph..

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University of Melbourne Researchers

Renwick Dobson Author

Michael Griffin Author

Michael Parker Author

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Grants

Awarded by Defense Threat Reduction Agency

Awarded by Australian Research Council

Funding Acknowledgements

This work was supported by Defense Threat Reduction Agency Contract W911NF-07-1-0105 and Australian Research Council Grants DP0770888 and LX0776388 for providing funding, an Australian postdoctoral fellowship (to M. A. P.) and a Federation fellowship (to M. W. P.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact.