1O99

CRYSTAL STRUCTURE OF THE S62A MUTANT OF PHOSPHOGLYCERATE MUTASE FROM BACILLUS STEAROTHERMOPHILUS COMPLEXED WITH 2-PHOSPHOGLYCERATE

Summary for 1O99

• Entry DOI: 10.2210/pdb1o99/pdb
• Related: 1EJJ 1EQJ 1O98
• Descriptor: 2,3-BISPHOSPHOGLYCERATE-INDEPENDENT PHOSPHOGLYCERATE MUTASE, MANGANESE (II) ION, 2-PHOSPHOGLYCERIC ACID, ... (5 entities in total)
• Functional Keywords: isomerase, alpha/beta-type structure
• Biological source: BACILLUS STEAROTHERMOPHILUS
• Total number of polymer chains: 1
• Total formula weight: 57824.93

Authors

Rigden, D.J.,Lamani, E.,Littlejohn, J.E.,Jedrzejas, M.J. (deposition date: 2002-12-11, release date: 2002-12-23, Last modification date: 2023-12-13)

Primary citation

Rigden, D.J.,Mello, L.V.,Lamani, E.,Littlejohn, J.E.,Jedrzejas, M.J.
Insights Into the Catalytic Mechanism of Cofactor-Independent Phosphoglycerate Mutase from X-Ray Crystallography, Simulated Dynamics and Molecular Modeling
J.Mol.Biol., 328:909-, 2003

PubMed Abstract: 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.

PubMed: 12729763
DOI: 10.1016/S0022-2836(03)00350-4

Experimental method

X-RAY DIFFRACTION (2.65 Å)