title: Structure of the PPX/GPPA phosphatase from Aquifex aeolicus in complex with the alarmone ppGpp.
abstract: The crystal structure of the prototype exopolyphosphatase/guanosine pentaphosphate phosphohydrolase protein family member from Aquifex aeolicus in complex with the intracellular second messenger guanosine tetraphosphate was determined at 2.7-A resolution. The hydrolytic base is identified as E119. The dual specificity established for the Escherichia coli homolog is shown to be compatible with a common active site for guanosine pentaphosphate and polyphosphate hydrolysis. Distinct and different degrees of closure between the two domains of the enzyme are associated with substrate binding. The arginines R22 and R267, residing in different domains, are crucial for guanosine pentaphosphate specificity as they interact with the unique 3'-ribose phosphorylation.
authors.affiliation: Biostructural Research, Department of Medicinal Chemistry, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. ok@farma.ku.dk
authors.forename: Ole
authors.initials: O
authors.lastname: Kristensen
authors.forename: Birthe
authors.initials: B
authors.lastname: Ross
authors.forename: Michael
authors.initials: M
authors.lastname: Gajhede
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D000595:Amino Acid Sequence; D001051:Apoenzymes / Q000737:chemistry; D001120:Arginine / Q000737:chemistry; D001419:Bacteria / Q000201:enzymology*; D001665:Binding Sites; D017124:Conserved Sequence; D003460:Crystallization; D018360:Crystallography, X-Ray; D006158:Guanosine Pentaphosphate / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D006159:Guanosine Tetraphosphate / Q000378:metabolism*; D006860:Hydrogen Bonding; D006868:Hydrolysis; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012984:Software; D013379:Substrate Specificity
chemical_list: D001051:Apoenzymes; D008024:Ligands; D006159:Guanosine Tetraphosphate; D006158:Guanosine Pentaphosphate; D001120:Arginine; D010744:Phosphoric Monoester Hydrolases; D017766:Acid Anhydride Hydrolases; C020137:exopolyphosphatase