Uridine kinase: altered enzyme with decreased affinities for uridine and CTP.

@article{Ropp1998UridineKA,
  title={Uridine kinase: altered enzyme with decreased affinities for uridine and CTP.},
  author={P. A. Ropp and T. Traut},
  journal={Archives of biochemistry and biophysics},
  year={1998},
  volume={359 1},
  pages={
          63-8
        }
}
  • P. A. Ropp, T. Traut
  • Published 1998
  • Biology, Medicine
  • Archives of biochemistry and biophysics
Uridine kinase is the rate-limiting enzyme in the salvage pathway for uridine or cytidine of mammalian cells. Alignment of the uridine kinase sequence with other nucleoside and nucleotide kinases supports a common ancestor for all of these. Three polypeptide segments for the ATP site and three polypeptide segments for the acceptor nucleoside site have been identified. We report here the characterization of an altered form of the enzyme with a single amino acid change, Q146R, within or near the… Expand
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References

SHOWING 1-10 OF 24 REFERENCES
Regulation of uridine kinase. Evidence for a regulatory site.
TLDR
It is proposed that the various effects of different ligands are best explained by the existence of a regulatory site (with more stringent specificity than the catalytic site) that controls dissociation of uridine kinase to the inactive monomer. Expand
Regulation of uridine kinase quaternary structure. Dissociation by the inhibitor CTP.
TLDR
Results imply that alteration of the enzyme's quaternary structure by normal effectors constitutes a mechanism for regulating uridine kinase activity in vivo. Expand
Substrate specificity and assembly of the catalytic center derived from two structures of ligated uridylate kinase.
TLDR
The relatively high side-activity of uridylate kinase for AMP is explained by the finding that the binding pocket is sized for an AMP, but constructed to bind UMP together with a water molecule. Expand
Cloning and expression of a cDNA encoding uridine kinase from mouse brain.
TLDR
The predicted secondary structure for uridine Kinase and the sequence comparison with three kinases having known crystal structures are consistent with uridine kinase having an alpha/beta core structure of the nucleotide-binding fold found in many kinases. Expand
Different affinity of the two forms of human cytosolic thymidine kinase towards pyrimidine analogs.
TLDR
The two forms of TK1 differ manyfold in affinity to the substrate ATP, to the inhibitor dTTP and to various analogs of thymidine substituted in the pyrimidine or sugar, and the kinetic reaction mechanisms suggest that the nucleoside analog. Expand
Homogeneous uridine kinase from Ehrlich ascites tumor: substrate specificity and inhibition by bisubstrate analogs.
TLDR
Uridine kinase has been purified to homogeneity from Ehrlich ascites tumor cells and shows substrate specificity only for ribopyrimidine nucleosides and is active with various analogs that have limited structural alterations; both endocyclic and exocyclics substituents can be acceptable. Expand
Uracil metabolism--UMP synthesis from orotic acid or uridine and conversion of uracil to beta-alanine: enzymes and cDNAs.
  • T. Traut, M. E. Jones
  • Biology, Medicine
  • Progress in nucleic acid research and molecular biology
  • 1996
TLDR
The biochemical roles of carnosine and other dipeptides containing β-alanine are discussed in the chapter, and nucleotides presumably exist at very low concentrations in the extracellular environment, though no values have been published for their concentration in blood. Expand
Uridine kinase from Ehrlich ascites carcinoma. Purification and properties of homogeneous enzyme.
TLDR
Multiple peaks of activity are routinely observed on ion exchange chromatography or gel filtration, for both crude preparations or homogeneous uridine kinase, in agreement with earlier results that this enzyme exists as multiple interconvertible oligomeric forms. Expand
Reversible ATP-dependent transition between two forms of human cytosolic thymidine kinase with different enzymatic properties.
TLDR
Results indicate that ATP is a positive effector of cytosolic thymidine kinase, controlling a kinetically slow transition between two molecular forms of the enzyme. Expand
Structure of the complex between adenylate kinase from Escherichia coli and the inhibitor Ap5A refined at 1.9 A resolution. A model for a catalytic transition state.
The structure of adenylate kinase from Escherichia coli ligated with the two-substrate-mimicking inhibitor P1,P5-bis(adenosine-5'-)pentaphosphate has been determined by X-ray diffraction and refinedExpand
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1
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3
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