1o99: Difference between revisions

Phosphoglycerate mutases catalyze the isomerization of 2 and, 3-phosphoglycerates, and are essential for glucose metabolism in most, organisms. Here, we further characterize the, 2,3-bisphosphoglycerate-independent phosphoglycerate mutase (iPGM) from, Bacillus stearothermophilus by determination of a high-resolution (1.4A), crystal structure of the wild-type enzyme and the crystal structure of its, S62A mutant. The mutant structure surprisingly showed the replacement of, one of the two catalytically essential manganese ions with a water, molecule, offering an additional possible explanation for its lack of, catalytic activity. Crystal structures invariably show substrate, phosphoglycerate to be entirely buried in a deep cleft between the two, iPGM domains. Flexibility analyses were therefore employed to reveal the, likely route of substrate access to the catalytic site through an aperture, created in the enzyme's surface during certain stages of the catalytic, process. Several conserved residues lining this aperture may contribute to, orientation of the substrate as it enters. Factors responsible for the, retention of glycerate within the phosphoenzyme structure in the proposed, mechanism are identified by molecular modeling of the glycerate complex of, the phosphoenzyme. Taken together, these results allow for a better, understanding of the mechanism of action of iPGMs. Many of the results are, relevant to a series of evolutionarily related enzymes. These studies will, facilitate the development of iPGM inhibitors which, due to the, demonstrated importance of this enzyme in many bacteria, would be of great, potential clinical significance.

1O99 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Geobacillus_stearothermophilus Geobacillus stearothermophilus] with MN, SO4 and 2PG as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphoglycerate_mutase Phosphoglycerate mutase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.4.2.1 5.4.2.1] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1O99 OCA].  

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