Contents

dUTP diphosphatase

dUTPase
crystal structures of feline immunodeficiency virus dutp pyrophosphatase and its nucleotide complexes in three crystal forms.
Identifiers
Symbol	dUTPase
Pfam	PF00692
Pfam clan	CL0153
InterPro	IPR008180
SCOP2	1dup / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

dUTPase_2
the crystal structure of a complex of campylobacter jejuni dutpase with substrate analogue dupnhp
Identifiers
Symbol	dUTPase_2
Pfam	PF08761
Pfam clan	CL0231
InterPro	IPR014871
SCOP2	1w2y / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

InEnzymology, a dUTP diphosphatase (EC 3.6.1.23) is an enzyme that catalyzes the chemical reaction

dUTP + H₂O${\displaystyle \rightleftharpoons }$ dUMP + diphosphate

Thus, the two substrates of this enzyme are dUTP and H₂O, whereas its two products are dUMP and diphosphate.

This enzyme belongs to the family of hydrolases, specifically those acting on acid anhydrides in phosphorus-containing anhydrides. The systematic name of this enzyme class is dUTP nucleotidohydrolase. Other names in common use include deoxyuridine-triphosphatase, dUTPase, dUTP pyrophosphatase, desoxyuridine 5'-triphosphate nucleotidohydrolase, and desoxyuridine 5'-triphosphatase. This enzyme participates in pyrimidine metabolism.

This enzyme has a dual function: on one hand, it removes dUTP from the deoxynucleotide pool, which reduces the probability of this base being incorporated into DNAbyDNA polymerases, while on the other hand, it produces the dTTP precursor dUMP. Lack or inhibition of dUTPase action leads to harmful perturbations in the nucleotide pool resulting in increased uracil content of DNA that activates a hyperactive futile cycle of DNA repair.^[1][2]

Structural studies[edit]

As of late 2007, 48 structures have been solved for this class of enzymes, with PDB accession codes 1DUC, 1DUD, 1DUN, 1DUP, 1DUT, 1EU5, 1EUW, 1F7D, 1F7K, 1F7N, 1F7O, 1F7P, 1F7Q, 1F7R, 1MQ7, 1OGH, 1OGK, 1OGL, 1PKH, 1PKJ, 1PKK, 1RN8, 1RNJ, 1SEH, 1SIX, 1SJN, 1SLH, 1SM8, 1SMC, 1SNF, 1SYL, 1VYQ, 1W2Y, 2BSY, 2BT1, 2CJE, 2D4L, 2D4M, 2D4N, 2HQU, 2HR6, 2HRM, 2OKB, 2OKD, 2OKE, 2OL0, 2OL1, and 2PY4.

There are at least two structurally distinct families of dUTPases. The crystal structureofhuman dUTPase reveals that each subunit of the dUTPase trimer folds into an eight-stranded jelly-roll beta barrel, with the C-terminal beta strands interchanged among the subunits. The structure is similar to that of the Escherichia coli enzyme, despite low sequence homology between the two enzymes.^[3]

The second family has a novel all-alpha fold, members of this family are unrelated to the all-beta fold found in dUTPases of the majority of organisms.^[4]

See also[edit]

• DUT, the gene that codes for this enzyme in humans
• DnaSordut, the gene that codes for this enzyme in E. coli

References[edit]

Further reading[edit]

• Bertani Le.; Haeggmark A.; Reichard P.; Interconversion of Deoxyuridine Phosphates (1963). "Enzymatic Synthesis of Deoxyribonucleotides. II. Formation". J. Biol. Chem. 238 (10): 3407–13. doi:10.1016/S0021-9258(18)48681-4. PMID 14085395.
• Giroir LE, Deutsch WA (1987). "Drosophila deoxyuridine triphosphatase. Purification and characterization". J. Biol. Chem. 262 (1): 130–4. doi:10.1016/S0021-9258(19)75898-0. PMID 3025197.
• Greenberg G, Somerville R (1962). "Deoxyuridylate Kinase Activity and Deoxyuridinetriphosphatase in Escherichia Coli". Proc. Natl. Acad. Sci. U.S.A. 48 (2): 247–57. Bibcode:1962PNAS...48..247G. doi:10.1073/pnas.48.2.247. PMC 220766. PMID 13901467.
• Grindey GR, Nichol CA (1971). "Mammalian deoxyuridine 5'-triphosphate pyrophosphatase". Biochim. Biophys. Acta. 240 (2): 180–3. doi:10.1016/0005-2787(71)90655-1. PMID 5105331.