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| - | ==DROSOPHILA MELANOGASTER DEOXYRIBONUCLEOSIDE KINASE SUCCESSFULLY ACTIVATES GEMCITABINE IN TRANSDUCED CANCER CELL LINES== | + | |
| - | <StructureSection load='2vpp' size='340' side='right' caption='[[2vpp]], [[Resolution|resolution]] 2.20Å' scene=''> | + | ==Drosophila melanogaster deoxyribonucleoside kinase successfully activates gemcitabine in transduced cancer cell lines== |
| | + | <StructureSection load='2vpp' size='340' side='right'caption='[[2vpp]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2vpp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Drome Drome]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VPP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2VPP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2vpp]] 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=2VPP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VPP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GEO:GEMCITABINE'>GEO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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">[[1zm7|1zm7]], [[2vp5|2vp5]], [[1zmx|1zmx]], [[2vp4|2vp4]], [[1j90|1j90]], [[2vp0|2vp0]], [[2jcs|2jcs]], [[1ot3|1ot3]], [[2vp6|2vp6]], [[1oe0|1oe0]], [[2vp2|2vp2]], [[2vp9|2vp9]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GEO:GEMCITABINE'>GEO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Deoxynucleoside_kinase Deoxynucleoside kinase], with EC number [http://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=2vpp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vpp OCA], [https://pdbe.org/2vpp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vpp RCSB], [https://www.ebi.ac.uk/pdbsum/2vpp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vpp ProSAT]</span></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=2vpp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vpp OCA], [http://pdbe.org/2vpp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2vpp RCSB], [http://www.ebi.ac.uk/pdbsum/2vpp PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vp/2vpp_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vp/2vpp_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Deoxynucleoside kinase]] | + | [[Category: Drosophila melanogaster]] |
| - | [[Category: Drome]] | + | [[Category: Large Structures]] |
| - | [[Category: Clausen, A]] | + | [[Category: Clausen A]] |
| - | [[Category: Gojkovic, Z]] | + | [[Category: Gojkovic Z]] |
| - | [[Category: Knecht, W]] | + | [[Category: Knecht W]] |
| - | [[Category: Mikkelsen, N E]] | + | [[Category: Mikkelsen NE]] |
| - | [[Category: Piskur, J]] | + | [[Category: Piskur J]] |
| - | [[Category: Willer, M]] | + | [[Category: Willer M]] |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Cancer]]
| + | |
| - | [[Category: Dna synthesis]]
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| - | [[Category: Gemcitabine]]
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| - | [[Category: Gene therapy]]
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| - | [[Category: Kinase]]
| + | |
| - | [[Category: Nucleoside analog]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Structure-function relationship]]
| + | |
| - | [[Category: Transferase]]
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| 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
Drosophila melanogaster multisubstrate deoxyribonucleoside kinase (Dm-dNK) can additionally sensitize human cancer cell lines towards the anti-cancer drug gemcitabine. We show that this property is based on the Dm-dNK ability to efficiently phosphorylate gemcitabine. The 2.2A resolution structure of Dm-dNK in complex with gemcitabine shows that the residues Tyr70 and Arg105 play a crucial role in the firm positioning of gemcitabine by extra interactions made by the fluoride atoms. This explains why gemcitabine is a good substrate for Dm-dNK.
Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine.,Knecht W, Mikkelsen NE, Clausen AR, Willer M, Eklund H, Gojkovic Z, Piskur J Biochem Biophys Res Commun. 2009 May 1;382(2):430-3. Epub 2009 Mar 13. PMID:19285960[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
- ↑ Knecht W, Mikkelsen NE, Clausen AR, Willer M, Eklund H, Gojkovic Z, Piskur J. Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine. Biochem Biophys Res Commun. 2009 May 1;382(2):430-3. Epub 2009 Mar 13. PMID:19285960 doi:http://dx.doi.org/10.1016/j.bbrc.2009.03.041
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