4il8

Crystal structure of an H329A mutant of p. aeruginosa PMM/PGM

spinqualitylabelsall models 4il8, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4il8 is a 1 chain structure with sequence from Pseae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, MG NonStd Res: SEP Related: 1k35, 1k2y, 1p5d, 1p5g, 1pcj Gene: algC, PA5322 (PSEAE) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ALGC_PSEAE] The phosphomannomutase activity produces a precursor for alginate polymerization. The alginate layer causes a mucoid phenotype and provides a protective barrier against host immune defenses and antibiotics. Also involved in core-LPS biosynthesis due to its phosphoglucomutase activity. Essential for rhamnolipid production, an exoproduct correlated with pathogenicity, and for biofilm production. Publication Abstract from PubMed Enzymes in the alpha-d-phosphohexomutase superfamily catalyze the conversion of 1-phosphosugars to their 6-phospho counterparts. Their phosphoryl transfer reaction has long been proposed to require general acid-base catalysts, but candidate residues for these key roles have not been identified. In this study, we show through mutagenesis and kinetic studies that a histidine (His329) in the active site is critical for enzyme activity in a well-studied member of the superfamily, phosphomannomutase/phosphoglucomutase from Pseudomonas aeruginosa. Crystallographic characterization of an H329A mutant protein showed no significant changes from the wild-type enzyme, excluding structural disruption as the source of its compromised activity. Mutation of the structurally analogous lysine residue in a related protein, phosphoglucomutase from Salmonella typhimurium, also results in significant catalytic impairment. Analyses of protein-ligand complexes of the P. aeruginosa enzyme show that His329 is appropriately positioned to abstract a proton from the O1/O6 hydroxyl of the phosphosugar substrates, and thus may serve as the general base in the reaction. Histidine is strongly conserved at this position in many proteins in the superfamily, and lysine is also often conserved at a structurally corresponding position, particularly in the phosphoglucomutase enzyme sub-group. These studies shed light on the mechanism of this important enzyme superfamily, and may facilitate the design of mechanism-based inhibitors. DATABASE: Structural data have been deposited in the Protein Data Bank with accession number 4IL8. Identification of an essential active-site residue in the alpha-D-phosphohexomutase enzyme superfamily.,Lee Y, Mehra-Chaudhary R, Furdui C, Beamer LJ FEBS J. 2013 Jun;280(11):2622-32. doi: 10.1111/febs.12249. Epub 2013 Apr 8. PMID:23517223 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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