Nucleotidyl transfer

The role of divalent cations in the mechanism of enzyme catalysed phosphoryl and nucleotidyl transfer reactions. A. S. Mildvan and C. M. Grisham, Struct. Bonding (Berlin), 1974,20,1-21 (88),... 

Catalyzed Phosphoryl and Nucleotidyl Transfer Reactions. - H. P. C. Hogenkamp,... 

Some of the polymerases exist as single polypeptide chains, while others function only as large complexes. In every case a two-metal ion catalytic mechanism with in-line nucleotidyl transfer,269 illustrated in Fig. 27-13, appears to be used by the enzymes.267 270 Two-metal ion catalysis is also observed for phosphatases and ribozymes (Chapter 12). 

Phosphoryl and nucleotidyl transfer enzymes are extremely important and widespread in biology. They have in common the catalysis of nucleophilic reactions of phosphorus esters, and the general requirement for divalent metal ions, particularly Mg11, for activity. This requirement has stimulated considerable interest in the catalytic roles of divalent metal ions in these reactions. 

This section emphasizes work done in the last few years. The reader is referred to other sources for reviews of older work236 or more general discussions of nucleophilic reactions at phosphorus.237"245 More general discussions of enzymic phosphoryl and nucleotidyl transfer are available,246 248 and the role of divalent metal ions has been reviewed.249"251... 

The mechanisms of nucleotide oligomer synthesis catalyzed by proteinoids have not reported. A tentative mechanism rests on the supposition that the proteinoid nucleotide complex is an intermediate of an enzyme-like nucleotidyl transfer reaction. 

Polynucleotide polymerases, or nucleotidyl transferases, are enzymes that catalyze the template-instructed polymerization of deoxyribo- or ribonu-cleoside triphosphates into polymeric nucleic acid - DNA or RNA. Depending on their substrate specificity, polymerases are classed as RNA- or DNA-dependent polymerases which copy their templates into RNA or DNA (all combinations of substrates are possible). Polymerization, or nucleotidyl transfer, involves formation of a phosphodiester bond that results from nucleophilic attack of the 3 -OH of primer-template on the a-phosphate group of the incoming nucleoside triphosphate. Although substantial diversity of sequence and function is observed for natural polymerases, there is evidence that many employ the same mechanism for DNA or RNA synthesis. On the basis of the crystal structures of polymerase replication complexes, a two-metal-ion mechanism of nucleotide addition was proposed [1] during this two divalent metal ions stabilize the structure and charge of the expected pentacovalent transition state (Figure B.16.1). 

Cherepanov AV, de Vries S (2002) Kinetic mechanism of the Mg2+-dependent nucleotidyl transfer catalyzed by T4 DNA and RNA... 

Contents A. S. Mildvan, C. M. Grisham The Role of Divalent Cations in the Mechanism of Enzyme Catalyzed Phosphoryl and Nucleotidyl Transfer Reactions. - H.P.C.Hogenkamp, G.N.Sando The Enzymatic Reduction of Ribonucleotides. - W. T. Oosterhuis The Electronic State of Iron in Some Natural Iron Compounds. Determination by Mossbauer and ESR Spectroscopy. - A. Trautwein Mossbauer Spectroscopy on Heme Proteins. 

Volume VIII Group Transfer, Part A Nucleotidyl Transfer, Nucleosidyl Transfer, Acyl Transfer, Phosphoryl Transfer... 

S. Shuman, Y. Liu, and B. Schwer. 1994. Covalent catalysis in nucleotidyl transfer reactions Essential motifs in Saccharomyces cerevisiae RNA capping enzyme are conserved in Schizosaccharomyces pombe and viral capping enzymes and among polynucleotide ligases Proc. Natl. Acad. Sci. U. S. A. 91 12046-12050. (PubMed) (Full Text in PMC)... 

Phosphoryl and nucleotidyl transfer reactions are nucleophilic displacements on phosphorus 3—6), and like analogous displacements on carbon (7) or on metal ions (5), have been found to take place by mechanisms varying between two extreme or limiting cases 1. In the dissociative or SnI mechanism the initial departure of the leaving nucleophile, yields the planar triply coordinate metaphosphate anion as a reactive chemical intermediate (3, 8), which then combines with the entering ligand on either face of the metaphosphate plane 2. In the associative... 

Substrate selection by polymerases determines, to a large extent, the accuracy of genomic replication. The efficiency of nucleotidyl transfer is dependent upon several interrelated factors. The two-metal-ion-dependent mechanism of polymerase catalysis appears to be universally conserved in most respects, with... 

Figure 14.7 Critical structures determined for nucleotidyl transfer catalyzed by Dpo4 (adapted with permission from [96], Figure 2, Copyright 2007, American Chemical...

Wang, L., Broyde, S., and Zhang, Y. (2009) Polymerase-tailored variations in the water-mediated and substrate-assisted mechanism for nucleotidyl transfer insights from a study of T7 DNA polymerase./. Mol. Biol, 389, 787-796. 

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