Structural Characterization of the Stringent Response Related Exopolyphosphatase/Guanosine Pentaphosphate Phosphohydrolase Protein Family

• Published in: Biochemistry (Easton) Vol. 43; no. 28; pp. 8894 - 8900
• Main Authors: Kristensen, Ole, Laurberg, Martin, Liljas, Anders, Kastrup, Jette Sandholm, Gajhede, Michael
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 20.07.2004
• Subjects: Acid Anhydride Hydrolases - chemistry; Adaptation, Physiological; Bacteria - enzymology; Bacterial Proteins - chemistry; Binding Sites; Biochemistry and Molecular Biology; Biokemi och molekylärbiologi; Biologi; Biological Sciences; Calcium; Chlorine; Crystallization; Crystallography, X-Ray; Models, Molecular; Molecular Structure; Natural Sciences; Naturvetenskap; Pyrophosphatases - chemistry
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi049083c

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 Å, 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.