Abstract
Deoxyuridine pyrophosphatase (dUTPase) cleaves the α-β phosphodiester bond of dUTP to form pyrophosphate and dUMP, preventing incorporation of uracil into DNA and providing the substrate for dTTP synthesis. Similar to other nucleotide binding proteins, dUTPase also consists of a sequence motif rich in glycine residues known as P-loop motif. The P-loop motif of the nucleotide binding proteins are involved in substrate binding, catalysis, recognition and regulation of activity. In dUTPase the function of the P-loop motif is not well understood. One of the main reasons for this limited information is the lack of the three-dimensional structure of a dUTPase enzyme with an ordered Gly-rich P-loop motif with a bound substrate and Mg2+ ion. This review presents an insight into the role of Gly-rich P-loop motif in the function of dUTPase as revealed from the crystal structure. The analysis reveals the Gly-rich P-loop motif of dUTPase to be the longest in terms of its amino-acid composition as compa red to other nucleotide binding proteins and exhibit a high-degree of sequence conservation among spectrum of species. The enzyme utilizes adaptive recognition to bind to the phosphate groups of the nucleotide. In particular, the α-β phosphodiester bond adopts an unfavorable eclipsed conformation in the presence of the Gly-rich P-loop motif. This conformation may be relevant to the mechanism of α-β phosphodiester bond cleavage.
Keywords: dTTP synthesis, dUTPase, Buchnera aphidicola
Current Protein & Peptide Science
Title: Glycine Rich P-loop Motif in Deoxyuridine Pyrophosphatase
Volume: 2 Issue: 4
Author(s): G. Sridhar Prasad
Affiliation:
Keywords: dTTP synthesis, dUTPase, Buchnera aphidicola
Abstract: Deoxyuridine pyrophosphatase (dUTPase) cleaves the α-β phosphodiester bond of dUTP to form pyrophosphate and dUMP, preventing incorporation of uracil into DNA and providing the substrate for dTTP synthesis. Similar to other nucleotide binding proteins, dUTPase also consists of a sequence motif rich in glycine residues known as P-loop motif. The P-loop motif of the nucleotide binding proteins are involved in substrate binding, catalysis, recognition and regulation of activity. In dUTPase the function of the P-loop motif is not well understood. One of the main reasons for this limited information is the lack of the three-dimensional structure of a dUTPase enzyme with an ordered Gly-rich P-loop motif with a bound substrate and Mg2+ ion. This review presents an insight into the role of Gly-rich P-loop motif in the function of dUTPase as revealed from the crystal structure. The analysis reveals the Gly-rich P-loop motif of dUTPase to be the longest in terms of its amino-acid composition as compa red to other nucleotide binding proteins and exhibit a high-degree of sequence conservation among spectrum of species. The enzyme utilizes adaptive recognition to bind to the phosphate groups of the nucleotide. In particular, the α-β phosphodiester bond adopts an unfavorable eclipsed conformation in the presence of the Gly-rich P-loop motif. This conformation may be relevant to the mechanism of α-β phosphodiester bond cleavage.
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Cite this article as:
Prasad Sridhar G., Glycine Rich P-loop Motif in Deoxyuridine Pyrophosphatase, Current Protein & Peptide Science 2001; 2 (4) . https://dx.doi.org/10.2174/1389203013381017
DOI https://dx.doi.org/10.2174/1389203013381017 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
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