1lvh
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The Structure of Phosphorylated beta-phosphoglucomutase from Lactoccocus lactis to 2.3 angstrom resolution
OverviewOverview
Phosphoglucomutases catalyze the interconversion of D-glucose 1-phosphate, and D-glucose 6-phosphate, a reaction central to energy metabolism in all, cells and to the synthesis of cell wall polysaccharides in bacterial, cells. Two classes of phosphoglucomutases (alpha-PGM and beta-PGM) are, distinguished on the basis of their specificity for alpha- and, beta-glucose-1-phosphate. beta-PGM is a member of the haloacid, dehalogenase (HAD) superfamily, which includes the sarcoplasmic, Ca(2+)-ATPase, phosphomannomutase, and phosphoserine phosphatase. beta-PGM, is unusual among family members in that the common phosphoenzyme, intermediate exists as a stable ground-state complex in this enzyme., Herein we report, for the first time, the three-dimensional structure of a, beta-PGM and the first view of the true phosphoenzyme intermediate in the, HAD superfamily. The crystal structure of the Mg(II) complex of, phosphorylated beta-phosphoglucomutase (beta-PGM) from Lactococcus lactis, has been determined to 2.3 A resolution by multiwavelength anomalous, diffraction (MAD) phasing on selenomethionine, and refined to an R(cryst), = 0.24 and R(free) = 0.28. The active site of beta-PGM is located between, the core and the cap domain and is freely solvent accessible. The residues, within a 6 A radius of the phosphorylated Asp8 include Asp10, Thr16, Ser114, Lys145, Glu169, and Asp170. The cofactor Mg(2+) is liganded with, octahedral coordination geometry by the carboxylate side chains of Asp8, Glu169, Asp170, and the backbone carbonyl oxygen of Asp10 along with one, oxygen from the Asp8-phosphoryl group and one water ligand. The phosphate, group of the phosphoaspartyl residue, Asp8, interacts with the side chains, of Ser114 and Lys145. The absence of a base residue near the aspartyl, phosphate group accounts for the persistence of the phosphorylated enzyme, under physiological conditions. Substrate docking shows that glucose-6-P, can bind to the active site of phosphorylated beta-PGM in such a way as to, position the C(1)OH near the phosphoryl group of the phosphorylated Asp8, and the C(6) phosphoryl group near the carboxylate group of Asp10. This, result suggests a novel two-base mechanism for phosphoryl group transfer, in a phosphorylated sugar.
About this StructureAbout this Structure
1LVH is a Single protein structure of sequence from Lactococcus lactis with MG as ligand. Active as Beta-phosphoglucomutase, with EC number 5.4.2.6 Full crystallographic information is available from OCA.
ReferenceReference
Caught in the act: the structure of phosphorylated beta-phosphoglucomutase from Lactococcus lactis., Lahiri SD, Zhang G, Dunaway-Mariano D, Allen KN, Biochemistry. 2002 Jul 2;41(26):8351-9. PMID:12081483
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