Structural highlights
1z4m is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , |
| Related: | 1z4i, 1z4j, 1z4k, 1z4l, 1z4p, 1z4q |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum |
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
The human mitochondrial deoxyribonucleotidase catalyzes the dephosphorylation of thymidine and deoxyuridine monophosphates and participates in the regulation of the dTTP pool in mitochondria. We present seven structures of the inactive D41N variant of this enzyme in complex with thymidine 3'-monophosphate, thymidine 5'-monophosphate, deoxyuridine 5'-monophosphate, uridine 5'-monophosphate, deoxyguanosine 5'-monophosphate, uridine 2'-monophosphate, and the 5'-monophosphate of the nucleoside analog 3'-deoxy 2'3'-didehydrothymidine, and we draw conclusions about the substrate specificity based on comparisons with enzyme activities. We show that the enzyme's specificity for the deoxyribo form of nucleoside 5'-monophosphates is due to Ile-133, Phe-49, and Phe-102, which surround the 2' position of the sugar and cause an energetically unfavorable environment for the 2'-hydroxyl group of ribonucleoside 5'-monophosphates. The close binding of the 3'-hydroxyl group of nucleoside 5'-monophosphates to the enzyme indicates that nucleoside analog drugs that are substituted with a bulky group at this position will not be good substrates for this enzyme.
Structural basis for substrate specificity of the human mitochondrial deoxyribonucleotidase.,Wallden K, Ruzzenente B, Rinaldo-Matthis A, Bianchi V, Nordlund P Structure. 2005 Jul;13(7):1081-8. PMID:16004879[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wallden K, Ruzzenente B, Rinaldo-Matthis A, Bianchi V, Nordlund P. Structural basis for substrate specificity of the human mitochondrial deoxyribonucleotidase. Structure. 2005 Jul;13(7):1081-8. PMID:16004879 doi:http://dx.doi.org/10.1016/j.str.2005.04.023
