PMID: 2506925Jul 25, 1989Paper

Active-site modification of mammalian DNA polymerase beta with pyridoxal 5'-phosphate: mechanism of inhibition and identification of lysine 71 in the deoxynucleoside triphosphate binding pocket

Biochemistry
A BasuM J Modak

Abstract

Pyridoxal 5'-phosphate is a potent inhibitor of the DNA polymerase activity of recombinant rat DNA polymerase beta. Kinetic studies indicate that the mechanism of PLP inhibition is complex. In a lower range of PLP concentration, inhibition is competitive with respect to substrate dNTP, whereas at higher levels of PLP several forms of enzyme combine with PLP and are involved in the overall inhibition, and a possible model for these interactions during the catalytic process is suggested. Reduction of the PLP-treated enzyme with sodium [3H]borohydride results in covalent incorporation of about 4 mol of PLP/mol of enzyme, and the modified enzyme is not capable of DNA polymerase activity. The presence of dNTP during the modification reaction blocks incorporation of 1 mol of PLP/mol of enzyme, and the enzyme so modified is almost fully active. This protective effect is not observed in the absence of template-primer. Tryptic peptide mapping of the PLP-modified enzyme reveals four major sites of modification. Of these four sites, only one is protected by dNTP from pyridoxylation. Sequence analysis of the tryptic peptide corresponding to the protected site reveals that it spans residues 68-80 in the amino acid sequence of the enzyme, wi...Continue Reading

References

Jul 24, 1979·Biochemistry·K TanabeS H Wilson
Jul 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·B Z ZmudzkaS H Wilson
Feb 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·J Shlomai, A Kornberg

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Citations

Aug 18, 2000·Mutation Research·W A Beard, S H Wilson
Jul 8, 1998·Mutation Research·S H Wilson
Jan 21, 2014·Biochimie·Ruslan Aphasizhev, Inna Aphasizheva
Jan 1, 1990·Bioconjugate Chemistry·G E Means, R E Feeney
Jun 17, 1998·The Journal of Biological Chemistry·R PrasadS H Wilson
Jul 26, 1996·The Journal of Biological Chemistry·C E PiersenR S Lloyd
Jun 26, 1998·Journal of Molecular Biology·R S TirumalaiA Landy

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