View source for 2vpp


==Drosophila melanogaster deoxyribonucleoside kinase successfully activates gemcitabine in transduced cancer cell lines==
<StructureSection load='2vpp' size='340' side='right' caption='[[2vpp]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== 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>
</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>
<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='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'>[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], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2vpp ProSAT]</span></td></tr>
</table>
== 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>  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <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>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2vpp ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== 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<ref>PMID:19285960</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2vpp" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Deoxynucleoside kinase]]
[[Category: Drome]]
[[Category: Clausen, A]]
[[Category: Gojkovic, Z]]
[[Category: Knecht, W]]
[[Category: Mikkelsen, N E]]
[[Category: Piskur, J]]
[[Category: Willer, M]]
[[Category: Atp-binding]]
[[Category: Cancer]]
[[Category: Dna synthesis]]
[[Category: Gemcitabine]]
[[Category: Gene therapy]]
[[Category: Kinase]]
[[Category: Nucleoside analog]]
[[Category: Nucleotide-binding]]
[[Category: Phosphoprotein]]
[[Category: Structure-function relationship]]
[[Category: Transferase]]