1hiy
|
BINDING OF NUCLEOTIDES TO NDP KINASE
OverviewOverview
The source of affinity for substrates of human nucleoside diphosphate, (NDP) kinases is particularly important in that its knowledge could be, used to design more effective antiviral nucleoside drugs (e.g., AZT). We, carried out a microcalorimetric study of the binding of enzymes from two, organisms to various nucleotides. Isothermal titration calorimetry has, been used to characterize the binding in terms of Delta G degrees, Delta H, degrees and Delta S degrees. Thermodynamic parameters of the interaction, of ADP with the hexameric NDP kinase from Dictyostelium discoideum and, with the tetrameric enzyme from Myxococcus xanthus, at 20 degrees C, were, similar and, in both cases, binding was enthalpy-driven. The interactions, of ADP, 2'deoxyADP, GDP, and IDP with the eukaryotic enzyme differed in, enthalpic and entropic terms, whereas the Delta G degrees values obtained, were similar due to enthalpy--entropy compensation. The binding of the, enzyme to nonphysiological nucleotides, such as AMP--PNP, 3'deoxyADP, and, 3'-deoxy-3'-amino-ADP, appears to differ in several respects., Crystallography of the protein bound to 3'-deoxy-3'-amino-ADP showed that, the drug was in a distorted position, and was unable to interact correctly, with active site side chains. The interaction of pyrimidine nucleoside, diphosphates with the hexameric enzyme is characterized by a lower, affinity than that with purine nucleotides. Titration showed the, stoichiometry of the interaction to be abnormal, with 9--12 binding, sites/hexamer. The presence of supplementary binding sites might have, physiological implications.
About this StructureAbout this Structure
1HIY is a Single protein structure of sequence from Dictyostelium discoideum with 3AN as ligand. Active as Nucleoside-diphosphate kinase, with EC number 2.7.4.6 Known structural/functional Sites: , and . Full crystallographic information is available from OCA.
ReferenceReference
Binding of nucleotides to nucleoside diphosphate kinase: a calorimetric study., Cervoni L, Lascu I, Xu Y, Gonin P, Morr M, Merouani M, Janin J, Giartosio A, Biochemistry. 2001 Apr 17;40(15):4583-9. PMID:11294625
Page seeded by OCA on Tue Dec 18 16:23:57 2007