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| | <StructureSection load='1z4l' size='340' side='right'caption='[[1z4l]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='1z4l' size='340' side='right'caption='[[1z4l]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1z4l]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z4L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Z4L FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1z4l]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z4L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Z4L FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TMP:THYMIDINE-5-PHOSPHATE'>TMP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1z4i|1z4i]], [[1z4j|1z4j]], [[1z4k|1z4k]], [[1z4m|1z4m]], [[1z4p|1z4p]], [[1z4q|1z4q]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TMP:THYMIDINE-5-PHOSPHATE'>TMP</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1z4l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z4l OCA], [http://pdbe.org/1z4l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1z4l RCSB], [http://www.ebi.ac.uk/pdbsum/1z4l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1z4l ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1z4l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z4l OCA], [https://pdbe.org/1z4l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1z4l RCSB], [https://www.ebi.ac.uk/pdbsum/1z4l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1z4l ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NT5M_HUMAN 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. | + | [https://www.uniprot.org/uniprot/NT5M_HUMAN 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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bianchi, V]] | + | [[Category: Bianchi V]] |
| - | [[Category: Nordlund, P]] | + | [[Category: Nordlund P]] |
| - | [[Category: Rinaldo-Matthis, A]] | + | [[Category: Rinaldo-Matthis A]] |
| - | [[Category: Ruzzenente, B]] | + | [[Category: Ruzzenente B]] |
| - | [[Category: Wallden, K]] | + | [[Category: Wallden K]] |
| - | [[Category: Alfa beta fold]]
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| - | [[Category: Hydrolase]]
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| 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
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
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