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.
Publication Abstract from PubMed
The human 5'(3')-deoxyribonucleotidases catalyze the dephosphorylation of deoxyribonucleoside monophosphates to the corresponding deoxyribonucleosides and thus help to maintain the balance between pools of nucleosides and nucleotides. Here, the structures of human cytosolic deoxyribonucleotidase (cdN) at atomic resolution (1.08 A) and mitochondrial deoxyribonucleotidase (mdN) at near-atomic resolution (1.4 A) are reported. The attainment of an atomic resolution structure allowed interatomic distances to be used to assess the probable protonation state of the phosphate anion and the side chains in the enzyme active site. A detailed comparison of the cdN and mdN active sites allowed the design of a cdN-specific inhibitor.
Structures of human cytosolic and mitochondrial nucleotidases: implications for structure-based design of selective inhibitors.,Pachl P, Fabry M, Rosenberg I, Simak O, Rezacova P, Brynda J Acta Crystallogr D Biol Crystallogr. 2014 Feb;70(Pt 2):461-70. doi:, 10.1107/S1399004713030502. Epub 2014 Jan 29. PMID:24531480[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Pachl P, Fabry M, Rosenberg I, Simak O, Rezacova P, Brynda J. Structures of human cytosolic and mitochondrial nucleotidases: implications for structure-based design of selective inhibitors. Acta Crystallogr D Biol Crystallogr. 2014 Feb;70(Pt 2):461-70. doi:, 10.1107/S1399004713030502. Epub 2014 Jan 29. PMID:24531480 doi:http://dx.doi.org/10.1107/S1399004713030502
