title: ATP-binding site of adenylate kinase: mechanistic implications of its homology with ras-encoded p21, F1-ATPase, and other nucleotide-binding proteins.
abstract: The MgATP binding site of adenylate kinase, located by a combination of NMR and x-ray diffraction, is near three protein segments, five to seven amino acids in length, that are homologous in sequence to segments found in other nucleotide-binding phosphotransferases, such as myosin and F1-ATPase, ras p21 and transducin GTPases, and cAMP-dependent and src protein kinases, suggesting equivalent mechanistic roles of these segments in all of these proteins. Segment 1 is a glycine-rich flexible loop that, on adenylate kinase, may control access to the ATP-binding site by changing its conformation. Segment 2 is an alpha-helix containing two hydrophobic residues that interact with the adenine-ribose moiety of ATP, and a lysine that may bind to the beta- and gamma-phosphates of ATP. Segment 3 is a hydrophobic strand of parallel beta-pleated sheet, terminated by a carboxylate, that flanks the triphosphate binding site. The various reported mutations of ras p21 that convert it to a transforming agent all appear to involve segment 1, and such substitutions may alter the properties of p21 by hindering a conformational change at this segment. In F1-ATPase, the flexible loop may, by its position, control both the accessibility and the ATP/ADP equilibrium constant on the enzyme.
authors.forename: D C
authors.initials: DC
authors.lastname: Fry
authors.forename: S A
authors.initials: SA
authors.lastname: Kuby
authors.forename: A S
authors.initials: AS
authors.lastname: Mildvan
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000263:Adenylate Kinase / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D008958:Models, Molecular; D009124:Muscle Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D010770:Phosphotransferases / Q000378:metabolism*; D011487:Protein Conformation; D016283:Proto-Oncogene Proteins p21(ras); D006180:Proton-Translocating ATPases / Q000378:metabolism; D011817:Rabbits; D012689:Sequence Homology, Nucleic Acid; D013552:Swine
chemical_list: D009124:Muscle Proteins; D009363:Neoplasm Proteins; D000255:Adenosine Triphosphate; D010770:Phosphotransferases; D000263:Adenylate Kinase; D006180:Proton-Translocating ATPases; D016283:Proto-Oncogene Proteins p21(ras)