Structural characterization of the stringent response related exopolyphosphatase/guanosine pentaphosphate phosphohydrolase protein family.
Exopolyphosphatase/guanosine pentaphosphate phosphohydrolase (PPX/GPPA) enzymes play central roles in the bacterial stringent response induced by starvation. The high-resolution crystal structure of the putative Aquifex aeolicus PPX/GPPA phosphatase from the actin-like ATPase domain superfamily has been determined, providing the first insights to features of the common catalytic core of the PPX/GPPA family. The protein has a two-domain structure with an active site located in the interdomain cleft. Two crystal forms were investigated (type I and II) at resolutions of 1.53 and 2.15 A, respectively. This revealed a structural flexibility that has previously been described as a "butterfly-like" cleft opening around the active site in other actin-like superfamily proteins. A calcium ion is observed at the center of this region in type I crystals, substantiating that PPX/GPPA enzymes use metal ions for catalysis. Structural analysis suggests that nucleotides bind at a similar position to that seen in other members of the superfamily.
Kristensen
Ole
O
Biostructural Research, Department of Medicinal Chemistry, The Danish University of Pharmaceutical Sciences, Universitetsparken 2, DK-2100 Copenhagen, Denmark. ok@dfuni.dk
Laurberg
Martin
M
Liljas
Anders
A
Kastrup
Jette Sandholm
JS
Gajhede
Michael
M
D017766:Acid Anhydride Hydrolases / Q000737:chemistry*; D000222:Adaptation, Physiological; D001419:Bacteria / Q000201:enzymology*; D001426:Bacterial Proteins / Q000737:chemistry; D001665:Binding Sites; D002118:Calcium; D002713:Chlorine; D003460:Crystallization; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D015394:Molecular Structure; D011755:Pyrophosphatases / Q000737:chemistry*
D001426:Bacterial Proteins; D002713:Chlorine; D017766:Acid Anhydride Hydrolases; D011755:Pyrophosphatases; C020137:exopolyphosphatase; C082499:guanosine-5'-triphosphate, 3'-diphosphate pyrophosphatase; D002118:Calcium