Structural highlights
Function
[NT5M_HUMAN] Dephosphorylates specifically the 5' and 2'(3')-phosphates of uracil and thymine deoxyribonucleotides, and so protects mitochondrial DNA replication from excess dTTP. Has only marginal activity towards dIMP and dGMP.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
5' nucleotidases are ubiquitous enzymes that dephosphorylate nucleoside monophosphates and participate in the regulation of nucleotide pools. The mitochondrial 5'-(3') deoxyribonucleotidase (dNT-2) specifically dephosphorylates dUMP and dTMP, thereby protecting mitochondrial DNA replication from excess dTTP. We have solved the structure of dNT-2, the first of a mammalian 5' nucleotidase. The structure reveals a relationship to the HAD family, members of which use an aspartyl nucleophile as their common catalytic strategy, with a phosphoserine phosphatase as the most similar neighbor. A structure-based sequence alignment of dNT-2 with other 5' nucleotidases also suggests a common origin for these enzymes. Here we study the structures of dNT-2 in complex with bound phosphate and beryllium trifluoride plus thymidine as model for a phosphoenzyme-product complex. Based on these structures, determinants for substrate specificity recognition and the catalytic action of dNT-2 are outlined.
Crystal structure of a human mitochondrial deoxyribonucleotidase.,Rinaldo-Matthis A, Rampazzo C, Reichard P, Bianchi V, Nordlund P Nat Struct Biol. 2002 Oct;9(10):779-87. PMID:12352955[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rinaldo-Matthis A, Rampazzo C, Reichard P, Bianchi V, Nordlund P. Crystal structure of a human mitochondrial deoxyribonucleotidase. Nat Struct Biol. 2002 Oct;9(10):779-87. PMID:12352955 doi:http://dx.doi.org/10.1038/nsb846
