title: Structure of the complex of yeast adenylate kinase with the inhibitor P1,P5-di(adenosine-5'-)pentaphosphate at 2.6 A resolution.
abstract: Adenylate kinase from yeast cytosol was crystallized as a 1:1 complex with the inhibitor P1,P5-di(adenosine-5'-)pentaphosphate. The crystalline structure was solved by multiple isomorphous replacement at a resolution of 3 A (1 A = 0.1 nm) and subsequent structural refinement at 2.6 A resolution. The yeast enzyme belongs to the group of large variants among the adenylate kinases, whereas the structurally known porcine cytosolic enzyme is a small variant. A comparison showed that the additional 31-residue segment of the large variants covers the active center. This had not been expected, because small and large variants show similar enzyme kinetics. Apart from this insertion, the chain folds of both adenylate kinases are the same. The yeast enzyme with bound inhibitor, however, assumes a much more closed form. In relation to the porcine enzyme without substrate, a segment of 28 residues containing two helices is rotated by about 30 degrees, closing the deep cleft at the active center. This corresponds to the expected induced fit. Sequence comparisons with other adenylate kinases suggest that one of the adenosine moieties of the inhibitor does not bind at a native nucleotide-binding site of the enzyme.
authors.affiliation: Institut für Organische Chemie und Biochemie, Freiburg, F.R.G.
authors.forename: U
authors.initials: U
authors.lastname: Egner
authors.forename: A G
authors.initials: AG
authors.lastname: Tomasselli
authors.forename: G E
authors.initials: GE
authors.lastname: Schulz
mesh_terms: D000227:Adenine Nucleotides / Q000494:pharmacology*; D000263:Adenylate Kinase / Q000037:antagonists & inhibitors*; D001665:Binding Sites; D003460:Crystallization; D015226:Dinucleoside Phosphates; D046911:Macromolecular Substances; D008958:Models, Molecular; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D014961:X-Ray Diffraction
chemical_list: D000227:Adenine Nucleotides; D015226:Dinucleoside Phosphates; D046911:Macromolecular Substances; C012275:P(1),P(5)-di(adenosine-5'-)pentaphosphate; D010770:Phosphotransferases; D000263:Adenylate Kinase