Nucleoside monophosphate kinases: structure, mechanism, and substrate specificity.
The catalytic mechanisms of adenylate kinase, guanylate kinase, uridylate kinase, and cytidylate kinase are reviewed in terms of kinetic and structural information that has been obtained in recent years. All four kinases share a highly related tertiary structure, characterized by a central five-stranded parallel beta-sheet with helices on both sides, as well as the three regions designated as the CORE, NMPbind, and LID domains. The catalytic mechanism continues to be refined to higher levels of resolution by iterative structure-function studies, and the strengths and limitations of site-directed mutagenesis are well illustrated in the case of adenylate kinase. The identity and roles of active site residues now appear to be resolved, and this review describes how specific site substitutions with unnatural amino acid side-chains have proven to be a major advance. Likewise, there is mounting evidence that phosphoryl transfer occurs by an associative transition state, based on (a) the stereochemical course of phosphoryl transfer, (b) geometric considerations, (c) examination of likely electronic distributions, (d) the orientation of the phosphoryl acceptor relative to the phosphoryl being transferred, (e) the most likely role of magnesium ion, (f) the lack of restricted access of solvent water, and (g) the results of oxygen-18 kinetic isotope. effect experiments.
Yan
H
H
Department of Biochemistry, Michigan State University, East Lansing 48824, USA.
Tsai
M D
MD
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009703:Nucleoside-Phosphate Kinase / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012265:Ribonucleotides / Q000378:metabolism; D016415:Sequence Alignment; D013379:Substrate Specificity
D012265:Ribonucleotides; D009703:Nucleoside-Phosphate Kinase