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Structure and Molecular Mechanism of Bacillus anthracis Cofactor-Independent Phosphoglycerate Mutase: A Crucial Enzyme for Spores and Growing Cells of Bacillus Species

Masatoshi Nukui ^*, Luciane V. Mello  , James E. Littlejohn ^*, Barbara Setlow , Peter Setlow , Kijeong Kim ^*, Terrance Leighton ^* and Mark J. Jedrzejas ^*

^* Children's Hospital Oakland Research Institute, Oakland, California 94609; Northwest Institute for Bio-Health Informatics/University of Liverpool, Liverpool L69 7ZB, United Kingdom; Embrapa Recursos Genéticos e Biotecnologia, Brasília, DF, Brazil; and Department of Molecular, Microbial and Structural Biology, University of Connecticut Health Center, Farmington, Connecticut 06030

Correspondence: Address reprint requests to Mark J. Jedrzejas, Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609. Tel.: 510-450-7932; Fax: 510-450-7914; E-mail: mjedrzejas{at}chori.org.

Phosphoglycerate mutases (PGMs) catalyze the isomerization of 2- and 3-phosphoglycerates 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 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 property 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.