Nucleotidylation

Nucleotidylation - the addition of adenylate-residues by Lnu enzymes - can also be the cause of resistance to lincosamide antibiotics in staphylococci and enterococci. A plasmid encoded ADP-ribosylating transferase (Arr-2) that leads to rifampicin resistance has been detected in various Enterobacteriaceae as well as in Pseudomonas aeruginosa. 

TUNEL is the name given to the in-situ DNA endlabelling technique which serves as a marker of apoptotic cells. This method is based on the specific binding of terminal de-oxy nucleotidyl transferases to the 3-hydroxy ends of DNA. The technique is normally used for examination under the light microscope but can also be adapted for examination under the electron microscope. 

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),... 

Mildvan AS, Grisham CM (1974) The Role of Divalent Cations in the Mechanism of Enzyme Catalyzed Phosphoryl and Nucleotidyl. 20 1-21 Mingos DMP, Hawes JC (1985) Complementary Spherical Electron Density Model. 63 1-63 Mingos DMP, Johnston RL (1987) Theoretical Models of Cluster Bonding. 68 29-87 Mingos DMP, McGrady JE, Rohl AL (1992) Moments of Inertia in Cluster and Coordination Compounds. 79 1-54... 

Mildvan, A. S., Grisham, CM. The Role of Divalent Cations in the Mechanism of Enzyme Catalyzed Phosphoryl and Nucleotidyl. Vol. 20, pp. 1-21. 

TCDD causes bone marrow hypocellularity, with specific decreases in the total number of hematopoietic stem cells (HSC) and lymphocyte precursors.42 16 Exposure to TCDD also diminishes mRNA levels of recombination activating gene-1 and terminal deoxy-nucleotidyl transferase in bone marrow cells.47 The best characterized effect of TCDD on bone marrow is the impaired maturation of B cells. A single dose of TCDD causes a transient, time- and dose-dependent, and developmental stage-specific impairment in B cell maturation, with mature B cells affected first, followed by depletion of B cell progenitors.45-46... 

Yet another super family, the nucleotidyl-transferase family, also utilizes two-metal-ion-dependent catalysis the members include transposases, retrovirus integrases and Holliday junction resolvases4. Whereas in the nucleases, the Mg2+ ions are asymmetrically coordinated, and play distinct roles, in activating the nucleophile and stabilizing the transition state, respectively, in the transposases, they are symmetrically coordinated and exchange roles to alternatively activate a water molecule and a 3 -OH for successive strand cleavage and transfer. 

Cytidine 5 -phospho-A-acetylneuraminate (298), the coenzyme of sialyltransferases, is a sugar-nucleotide in which the leaving group is a nucleotidyl monophosphate that contains a carboxylate group directly attached to the anomeric centre. Studies of its hydrolysis reveal that at pH 5 specific acid catalysis occurs (Scheme 34) to yield a glycosyl carbocation as a tight ion pair, the lifetime of which was estimated... 

The enzymes that synthesise RNA and DNA are known as nucleic acid polymerases. They are classified as nucleotidyl transferases (Chapter 3). The basic reaction can be represented as follows ... 

Aminoglycosides Gentamicin Streptomycin Spectinomycin Phosphorylation Acetylation Nucleotidylation Efflux Altered target... 

StrD/BlmD 355 16736 dTDP-D-glucose synthase/nucleotidyl-transferase... 

A metal-nucleotide complex that exhibits low rates of ligand exchange as a result of substituting higher oxidation state metal ions with ionic radii nearly equal to the naturally bound metal ion. Such compounds can be prepared with chromium(III), cobalt(III), and rhodi-um(III) in place of magnesium or calcium ion. Because these exchange-inert complexes can be resolved into their various optically active isomers, they have proven to be powerful mechanistic probes, particularly for kinases, NTPases, and nucleotidyl transferases. In the case of Cr(III) coordination complexes with the two phosphates of ATP or ADP, the second phosphate becomes chiral, and the screw sense must be specified to describe the three-dimensional configuration of atoms. 

This enzyme [EC 2.7.7.46] catalyzes the reaction of a nucleoside triphosphate with gentamicin to produce a 2"-nucleotidylgentamicin and pyrophosphate (or, diphosphate). The nucleoside triphosphate can be ATP, dATP, CTP, ITP, or GTP. Kanamycin, tobramycin, and sisomicin can also act as the acceptor substrate. The nucleotidyl residue is transferred to the 2-hydroxyl group of the 3-amino-3-deoxy-D-glucose moiety in the acceptor substrate. 

The systematic name for these enzymes is nucleoside triphosphate a-D-glycosyl phosphate-nucleotidyl transferases (E.C. 2.7.7 group). 

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

Like phosphate, the nucleotidyl group (UMP or AMP, for example) is an excellent leaving group, facilitating nucleophilic attack by activating the sugar carbon to which it is attached. 

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). 

Glycosyl—Enzyme Complex Intermediates in Biosynthesis of Complex Saccharides. The synthesis of nucleoside diphosphate sugars involves the transfer of a nucleotidyl group from a nucleoside triphosphate to a sugar 1-phosphate with the simultaneous release of pyrophosphate according to the following general reaction (11) ... 

Studies on the kinetic behaviour of nucleoside and nucleotide complexes are less common than those on structural aspects. This arises because of the rapid rates of the formation and dissociation reactions, requiring NMR or temperature-jump relaxation measurements. The number of species that can coexist in solution also hinders interpretation. The earlier kinetic studies have been reviewed by Frey and Stuehr.127 Two important biological reactions of the nucleotides are phosphoryl and nucleotidyl group transfers. Both reactions are catalytic nucleophilic reactions and they both require the presence of a divalent metal ion, in particular Mg2+. Consequently, one of the main interests has been in understanding the catalytic mechanism of the metal ion involvement. This has mainly involved studies on related non-enzymic reactions.128... 

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