1o98: Difference between revisions
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==Overview== | ==Overview== | ||
Phosphoglycerate mutases catalyze the isomerization of 2 and | 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. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Phosphoglycerate mutase]] | [[Category: Phosphoglycerate mutase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Jedrzejas, M | [[Category: Jedrzejas, M J.]] | ||
[[Category: Lamani, E.]] | [[Category: Lamani, E.]] | ||
[[Category: Littlejohn, J | [[Category: Littlejohn, J E.]] | ||
[[Category: Rigden, D | [[Category: Rigden, D J.]] | ||
[[Category: 2PG]] | [[Category: 2PG]] | ||
[[Category: MN]] | [[Category: MN]] | ||
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[[Category: isomerase]] | [[Category: isomerase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:14:58 2008'' | ||
Revision as of 15:14, 21 February 2008
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1.4A CRYSTAL STRUCTURE OF PHOSPHOGLYCERATE MUTASE FROM BACILLUS STEAROTHERMOPHILUS COMPLEXED WITH 2-PHOSPHOGLYCERATE
OverviewOverview
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.
About this StructureAbout this Structure
1O98 is a Single protein structure of sequence from Geobacillus stearothermophilus with , and as ligands. Active as Phosphoglycerate mutase, with EC number 5.4.2.1 Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
Insights into the catalytic mechanism of cofactor-independent phosphoglycerate mutase from X-ray crystallography, simulated dynamics and molecular modeling., Rigden DJ, Lamani E, Mello LV, Littlejohn JE, Jedrzejas MJ, J Mol Biol. 2003 May 9;328(4):909-20. PMID:12729763
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