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Structures of an alanine racemase from Bacillus anthracis (BA0252) in the presence and absence of (R)-1-amino­ethylphosphonic acid (L-Ala-P)

DOI: 10.1107/S1744309108007252 DOI Help

Authors: Kinfai Au (Oxford University) , Jingshan Ren (Oxford University) , Thomas S. Walter (University of Oxford) , Karl Harlos (Oxford University) , Joanne E. Nettleship (Oxford University) , Raymond J. Owens (Oxford University) , David I. Stuart (Oxford University) , Robert M. Esnouf (Oxford University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acta Crystallographica Section F Structural Biology And Crystallization Communications , VOL 64 , PAGES 327-333

State: Published (Approved)
Published: April 2008

Abstract: Bacillus anthracis, the causative agent of anthrax, has been targeted by the Oxford Protein Production Facility to validate high-throughput protocols within the Structural Proteomics in Europe project. As part of this work, the structures of an alanine racemase (BA0252) in the presence and absence of the inhibitor (R)-1-aminoethylphosphonic acid (L-Ala-P) have determined by X-ray crystallo­graphy to resolutions of 2.1 and 1.47 Å, respectively. Difficulties in crystallizing this protein were overcome by the use of reductive methylation. Alanine racemase has attracted much interest as a possible target for anti-anthrax drugs: not only is D-alanine a vital component of the bacterial cell wall, but recent studies also indicate that alanine racemase, which is accessible in the exosporium, plays a key role in inhibition of germination in B. anthracis. These structures confirm the binding mode of L-Ala-P but suggest an unexpected mechanism of inhibition of alanine racemase by this compound and could provide a basis for the design of improved alanine racemase inhibitors with potential as anti-anthrax therapies.

Journal Keywords: D-alanine; L-alanine; germination; inhibition; pyridoxal 5′-phosphate; reductive methylation

Subject Areas: Biology and Bio-materials

Facility: BM14 at ESRF

Added On: 14/05/2010 10:34

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Structural biology Life Sciences & Biotech

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