The reaction of phosphohexomutase from Pseudomonas aeruginosa: structural insights into a simple processive enzyme.
The enzyme phosphomannomutase/phosphoglucomutase (PMM/PGM) from Pseudomonas aeruginosa catalyzes the reversible conversion of 1-phospho to 6-phospho-sugars. The reaction entails two phosphoryl transfers, with an intervening 180 degrees reorientation of the reaction intermediate (e.g. glucose 1,6-bisphosphate) during catalysis. Reorientation of the intermediate occurs without dissociation from the active site of the enzyme and is, thus, a simple example of processivity, as defined by multiple rounds of catalysis without release of substrate. Structural characterization of two PMM/PGM-intermediate complexes with glucose 1,6-bisphosphate provides new insights into the reaction catalyzed by the enzyme, including the reorientation of the intermediate. Kinetic analyses of site-directed mutants prompted by the structural studies reveal active site residues critical for maintaining association with glucose 1,6-bisphosphate during its unique dynamic reorientation in the active site of PMM/PGM.
Regni
Catherine
C
Department of Biochemistry, University of Missouri, Columbia, Missouri 65211, USA.
Schramm
Andrew M
AM
Beamer
Lesa J
LJ
D002384:Catalysis; D020134:Catalytic Domain / Q000235:genetics; D018360:Crystallography, X-Ray; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives / Q000378:metabolism; D006860:Hydrogen Bonding; D007700:Kinetics; D008954:Models, Biological; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D010733:Phosphoglucomutase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017875:Phosphotransferases (Phosphomutases) / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055672:Static Electricity; D013379:Substrate Specificity
D011994:Recombinant Proteins; D019298:Glucose-6-Phosphate; C016473:glucose-1,6-bisphosphate; D017875:Phosphotransferases (Phosphomutases); D010733:Phosphoglucomutase; C052799:phosphomannomutase