The NIAID-supported Seattle Structural Genomics Center for Infectious Disease (SSGCID) has determined several structures of a phosphoglycerate mutase, or PGAM, enzyme from Burkholderia pseudomallei, a pathogen that causes the serious skin infection melioidosis. The structures are significant because they provide a comprehensive picture of the function of the enzyme and could form the basis for structure-based drug design.
The PGAM enzyme family includes enzymes that can catalyze the conversion of 3-phosphoglycerate to 2-phosphoglycerate or 2-phosphoglycerate to 3-phosphoglycerate. This reaction is used by many organisms to convert glucose into energy.
The Center has solved six X-ray crystal structures of PGAM from B. pseudomallei bound to various ligands, including both its substrate, which is the molecule PGAM acts upon, and other small molecules whose binding can help understand the enzymes mechanisms. A single crystal structure provides just a snapshot of the dynamic mechanism of an enzyme. The ensemble of six X-ray crystal structures of B. pseudomallei PGAM provides, for the first time, a comprehensive view of a PGAM enzyme mechanism. Taken together, these crystal structures allow the definitive identification of key amino-acid residues involved in substrate binding and enzyme action. The solution of these structures bound to these different compounds provides a starting point for elucidating mode of action and thereby helps in the design of small molecule inhibitors that could possibly go on to become a therapeutic.
Shown below is PGAM bound to one of these small molecules. For more information please visit the Protein Data Bank entries: The unbound structure (3ezn), and the structure bound to various molecules 3fdz,3gw8, 3gp5, 3fdz, 3lnt and 3gp3 (shown below).
Crystal structure of phosphoglyceromutase from Burkholderia pseudomallei bound to the fragment 2-phosphoserine
Davies D, Staker B, Abendroth J, Edwards T, Hartley R, Leonard J, Kim H, Rychel AL, Hewitt SN, Myler PJ, Stewart LJ. An ensemble of structures of Burkholderia pseudomallei 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase. Acta Cryst. (2011) F67, 9:1044-1050 (PDF). PMID: 21904048.
All featured structures from the NIAID Structural Genomics Centers
Last Updated August 08, 2012
Last Reviewed August 08, 2012