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| | <StructureSection load='1oe0' size='340' side='right'caption='[[1oe0]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='1oe0' size='340' side='right'caption='[[1oe0]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1oe0]] is a 4 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=1OE0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1OE0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1oe0]] is a 4 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=1OE0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OE0 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=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</scene></td></tr> | + | </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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1j90|1j90]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1j90|1j90]]</div></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='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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1oe0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oe0 OCA], [http://pdbe.org/1oe0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1oe0 RCSB], [http://www.ebi.ac.uk/pdbsum/1oe0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1oe0 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=1oe0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oe0 OCA], [https://pdbe.org/1oe0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1oe0 RCSB], [https://www.ebi.ac.uk/pdbsum/1oe0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1oe0 ProSAT]</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]] |
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| | </div> | | </div> |
| | <div class="pdbe-citations 1oe0" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 1oe0" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Thymidine kinase|Thymidine kinase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| 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
Deoxyribonucleoside kinases are feedback inhibited by the final products of the salvage pathway, the deoxyribonucleoside triphosphates. In the present study, the mechanism of feedback inhibition is presented based on the crystal structure of a complex between the fruit fly deoxyribonucleoside kinase and its feedback inhibitor deoxythymidine triphosphate. The inhibitor was found to be bound as a bisubstrate inhibitor with its nucleoside part in the nucleoside binding site and with its phosphate groups partially occupying the phosphate donor site. The overall structure of the enzyme--inhibitor complex is very similar to the enzyme--substrate complexes with deoxythymidine and deoxycytidine, except for a conformational change within a region otherwise directly involved in catalysis. This conformational change involves a magnesium ion, which is coordinated in the inhibitor complex to the phosphates and to the primary base, Glu52, that normally is positioned close to the 5'-OH of the substrate deoxyribose.
Structural basis for feedback inhibition of the deoxyribonucleoside salvage pathway: studies of the Drosophila deoxyribonucleoside kinase.,Mikkelsen NE, Johansson K, Karlsson A, Knecht W, Andersen G, Piskur J, Munch-Petersen B, Eklund H Biochemistry. 2003 May 20;42(19):5706-12. PMID:12741827[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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, Johansson K, Karlsson A, Knecht W, Andersen G, Piskur J, Munch-Petersen B, Eklund H. Structural basis for feedback inhibition of the deoxyribonucleoside salvage pathway: studies of the Drosophila deoxyribonucleoside kinase. Biochemistry. 2003 May 20;42(19):5706-12. PMID:12741827 doi:http://dx.doi.org/10.1021/bi0340043
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