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| | <StructureSection load='2vp0' size='340' side='right'caption='[[2vp0]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='2vp0' size='340' side='right'caption='[[2vp0]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2vp0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Drome Drome]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VP0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VP0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2vp0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VP0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VP0 FirstGlance]. <br> |
| - | </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=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</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]] 2.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1zm7|1zm7]], [[2jcs|2jcs]], [[1ot3|1ot3]], [[1oe0|1oe0]], [[1zmx|1zmx]], [[1j90|1j90]]</div></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=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Deoxynucleoside_kinase Deoxynucleoside kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.145 2.7.1.145] </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=2vp0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vp0 OCA], [https://pdbe.org/2vp0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vp0 RCSB], [https://www.ebi.ac.uk/pdbsum/2vp0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vp0 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=2vp0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vp0 OCA], [https://pdbe.org/2vp0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vp0 RCSB], [https://www.ebi.ac.uk/pdbsum/2vp0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vp0 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/DNK_DROME DNK_DROME]] Deoxyribonucleoside kinase that has a broad specificity phosphorylating thymidine, deoxyadenosine, deoxycytidine and deoxyguanosine. Specificity is higher for pyrimidine nucleosides. Several anti-viral and anti-cancer nucleoside analogs are also efficiently phosphorylated.<ref>PMID:10446143</ref> <ref>PMID:10692477</ref> <ref>PMID:16008571</ref>
| + | [https://www.uniprot.org/uniprot/DNK_DROME DNK_DROME] Deoxyribonucleoside kinase that has a broad specificity phosphorylating thymidine, deoxyadenosine, deoxycytidine and deoxyguanosine. Specificity is higher for pyrimidine nucleosides. Several anti-viral and anti-cancer nucleoside analogs are also efficiently phosphorylated.<ref>PMID:10446143</ref> <ref>PMID:10692477</ref> <ref>PMID:16008571</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </div> | | </div> |
| | <div class="pdbe-citations 2vp0" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 2vp0" style="background-color:#fffaf0;"></div> |
| - | | |
| - | ==See Also== | |
| - | *[[Thymidine kinase|Thymidine kinase]] | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Deoxynucleoside kinase]] | + | [[Category: Drosophila melanogaster]] |
| - | [[Category: Drome]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Eklund, H]] | + | [[Category: Eklund H]] |
| - | [[Category: Mikkelsen, N E]] | + | [[Category: Mikkelsen NE]] |
| - | [[Category: Munch-Petersen, B]] | + | [[Category: Munch-Petersen B]] |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Deoxyribonucleoside kinase]]
| + | |
| - | [[Category: Dna synthesis]]
| + | |
| - | [[Category: Drosophila]]
| + | |
| - | [[Category: Dttp]]
| + | |
| - | [[Category: Feedback inhibition]]
| + | |
| - | [[Category: Kinase]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Salvage pathway]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
DNK_DROME Deoxyribonucleoside kinase that has a broad specificity phosphorylating thymidine, deoxyadenosine, deoxycytidine and deoxyguanosine. Specificity is higher for pyrimidine nucleosides. Several anti-viral and anti-cancer nucleoside analogs are also efficiently phosphorylated.[1] [2] [3]
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 Drosophila melanogaster multisubstrate deoxyribonucleoside kinase (dNK; EC 2.7.1.145) has a high turnover rate and a wide substrate range that makes it a very good candidate for gene therapy. This concept is based on introducing a suicide gene into malignant cells in order to activate a prodrug that eventually may kill the cell. To be able to optimize the function of dNK, it is vital to have structural information of dNK complexes. In this study we present crystal structures of dNK complexed with four different nucleoside analogs (floxuridine, brivudine, zidovudine and zalcitabine) and relate them to the binding of substrate and feedback inhibitors. dCTP and dGTP bind with the base in the substrate site, similarly to the binding of the feedback inhibitor dTTP. All nucleoside analogs investigated bound in a manner similar to that of the pyrimidine substrates, with many interactions in common. In contrast, the base of dGTP adopted a syn-conformation to adapt to the available space of the active site.
Structural studies of nucleoside analog and feedback inhibitor binding to Drosophila melanogaster multisubstrate deoxyribonucleoside kinase.,Mikkelsen NE, Munch-Petersen B, Eklund H FEBS J. 2008 May;275(9):2151-60. Epub 2008 Apr 1. PMID:18384378[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Johansson M, van Rompay AR, Degreve B, Balzarini J, Karlsson A. Cloning and characterization of the multisubstrate deoxyribonucleoside kinase of Drosophila melanogaster. J Biol Chem. 1999 Aug 20;274(34):23814-9. PMID:10446143
- ↑ Munch-Petersen B, Knecht W, Lenz C, Sondergaard L, Piskur J. Functional expression of a multisubstrate deoxyribonucleoside kinase from Drosophila melanogaster and its C-terminal deletion mutants. J Biol Chem. 2000 Mar 3;275(9):6673-9. PMID:10692477
- ↑ Welin M, Skovgaard T, Knecht W, Zhu C, Berenstein D, Munch-Petersen B, Piskur J, Eklund H. Structural basis for the changed substrate specificity of Drosophila melanogaster deoxyribonucleoside kinase mutant N64D. FEBS J. 2005 Jul;272(14):3733-42. PMID:16008571 doi:10.1111/j.1742-4658.2005.04803.x
- ↑ Mikkelsen NE, Munch-Petersen B, Eklund H. Structural studies of nucleoside analog and feedback inhibitor binding to Drosophila melanogaster multisubstrate deoxyribonucleoside kinase. FEBS J. 2008 May;275(9):2151-60. Epub 2008 Apr 1. PMID:18384378 doi:http://dx.doi.org/10.1111/j.1742-4658.2008.06369.x
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