title: Complexes of the enzyme phosphomannomutase/phosphoglucomutase with a slow substrate and an inhibitor.
abstract: Two complexes of the enzyme phosphomannomutase/phosphoglucomutase (PMM/PGM) from Pseudomonas aeruginosa with a slow substrate and with an inhibitor have been characterized by X-ray crystallography. Both ligands induce an interdomain rearrangement in the enzyme that creates a highly buried active site. Comparisons with enzyme-substrate complexes show that the inhibitor xylose 1-phosphate utilizes many of the previously observed enzyme-ligand interactions. In contrast, analysis of the ribose 1-phosphate complex reveals a combination of new and conserved enzyme-ligand interactions for binding. The ability of PMM/PGM to accommodate these two pentose phosphosugars in its active site may be relevant for future efforts towards inhibitor design.
authors.affiliation: Department of Structural Biology, St Jude Children's Research Hospital, 332 North Lauderdale M/S 311, Memphis, TN 38105, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Regni
authors.forename: Grant S
authors.initials: GS
authors.lastname: Shackelford
authors.forename: Lesa J
authors.initials: LJ
authors.lastname: Beamer
mesh_terms: D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D008958:Models, Molecular; D010428:Pentosephosphates / Q000737:chemistry / Q000494:pharmacology; D010733:Phosphoglucomutase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D017875:Phosphotransferases (Phosphomutases) / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D012267:Ribosemonophosphates / Q000737:chemistry / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D008024:Ligands; D010428:Pentosephosphates; D012267:Ribosemonophosphates; C031154:ribose 1-phosphate; C054739:xylose 1-phosphate; D017875:Phosphotransferases (Phosphomutases); D010733:Phosphoglucomutase; C052799:phosphomannomutase