title: Crystal structure and substrate specificity of the thermophilic serine:pyruvate aminotransferase from Sulfolobus solfataricus.
abstract: The three-dimensional structure of the Sulfolobus solfataricus serine:pyruvate aminotransferase has been determined to 1.8 Å resolution. The structure of the protein is a homodimer that adopts the type I fold of pyridoxal 5'-phosphate (PLP)-dependent aminotransferases. The structure revealed the PLP cofactor covalently bound in the active site to the active-site lysine in the internal aldimine form. The structure of the S. solfataricus enzyme was also determined with an amino form of the cofactor pyridoxamine 5'-phosphate bound in the active site and in complex with gabaculine, an aminotransferase inhibitor. These structures showed the changes in the enzyme active site during the course of the catalytic reaction. A comparison of the structure of the S. solfataricus enzyme with that of the closely related alanine:glyoxylate aminotransferase has identified structural features that are proposed to be responsible for the differences in substrate specificity between the two enzymes. These results have been complemented by biochemical studies of the substrate specificity and thermostability of the S. solfataricus enzyme.
authors: Henry Wellcome Building for Biocatalysis, Biosciences, College of Life and Environmental Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, England.
authors: Christopher
authors: C
authors: Sayer
authors: Martin
authors: M
authors: Bommer
authors: Michail
authors: M
authors: Isupov
authors: John
authors: J
authors: Ward
authors: Jennifer
authors: J
authors: Littlechild
mesh_terms: D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008958:Models, Molecular; D011732:Pyridoxal Phosphate / Q000378:metabolism; D013379:Substrate Specificity; D048229:Sulfolobus solfataricus / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D000637:Transaminases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D003509:Cyclohexanecarboxylic Acids; D004791:Enzyme Inhibitors; C012987:gabaculine; D011732:Pyridoxal Phosphate; D000637:Transaminases; C022638:serine-pyruvate aminotransferase