Structure and Molecular Mechanism of Bacillus anthracis
Cofactor-independent Phosphoglycerate Mutase, a Crucial
Enzyme for Spores and Growing Cells of Bacillus Species
Masatoshi Nukui 1, Luciane V Mello 2, James E Littlejohn 1, Barbara Setlow 3, Peter Setlow 3, Kijeong Kim 1, Terrance Leighton 1 and Mark J Jedrzejas 1*
1 Children's Hospital Oakland Research Institute
2 NIBHI/University of Liverpool
3 University of Connecticut Health Center
* To whom correspondence should be addressed. E-mail: mjedrzejas{at}chori.org.
Submitted on July 24, 2006
Revised on August 23, 2006
Accepted on 13 October 2006
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Abstract |
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Phosphoglycerate mutases (PGMs) catalyze the isomerization of 2- and 3-phosphoglycerates (2-, 3PGA) and are essential for glucose metabolism in most organisms. This study reports the production, structure and molecular dynamics analysis of Bacillus anthracis cofactor independent PGM (iPGM). The three-dimensional structure of B. anthracis PGM is composed of two structural and functional domains, the phosphatase and transferase. The structural relationship between these two domains is somewhat different than in the B. stearothermophilus iPGM structure determined previously. However, the structures of the two domains of B. anthracis iPGM show a high degree of similarity to those in B. stearothermophilus iPGM. The novel domain arrangement in B. anthracis iPGM and the dynamic behavior of these domains is directly linked to the mechanism of enzyme catalysis, in which substrate binding is proposed to result in close association of the two domains. The structure of B. anthracis iPGM and the molecular dynamics of this structure provide unique insight into the mechanism of iPGM catalysis, in particular the roles of changes in coordination geometry of the enzyme's two bivalent metal ions and the regulation of this enzyme's activity by changes in intracellular pH during spore formation and germination in Bacillus species.
Key Words:
Gram-positive bacteria, catalysis, catalytic mechanism, glycolysis, phosphoglycerate mutase, spores
