1p60

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(New page: 200px<br /> <applet load="1p60" size="450" color="white" frame="true" align="right" spinBox="true" caption="1p60, resolution 1.96&Aring;" /> '''Structure of human ...)
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[[Image:1p60.gif|left|200px]]<br />
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==Structure of human dCK complexed with 2'-Deoxycytidine and ADP, Space group C 2 2 21==
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<applet load="1p60" size="450" color="white" frame="true" align="right" spinBox="true"
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<StructureSection load='1p60' size='340' side='right' caption='[[1p60]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
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caption="1p60, resolution 1.96&Aring;" />
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== Structural highlights ==
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'''Structure of human dCK complexed with 2'-Deoxycytidine and ADP, Space group C 2 2 21'''<br />
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<table><tr><td colspan='2'>[[1p60]] is a 2 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=1P60 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1P60 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=DCZ:2-DEOXYCYTIDINE'>DCZ</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1p5z|1p5z]], [[1p61|1p61]], [[1p62|1p62]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DCK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Deoxycytidine_kinase Deoxycytidine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.74 2.7.1.74] </span></td></tr>
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<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=1p60 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p60 OCA], [http://pdbe.org/1p60 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1p60 RCSB], [http://www.ebi.ac.uk/pdbsum/1p60 PDBsum]</span></td></tr>
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</table>
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== Function ==
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[[http://www.uniprot.org/uniprot/DCK_HUMAN DCK_HUMAN]] Required for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). Has broad substrate specificity, and does not display selectivity based on the chirality of the substrate. It is also an essential enzyme for the phosphorylation of numerous nucleoside analogs widely employed as antiviral and chemotherapeutic agents.<ref>PMID:18377927</ref> <ref>PMID:20614893</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/p6/1p60_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Human deoxycytidine kinase (dCK) phosphorylates the natural deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA) and is an essential enzyme for the phosphorylation of numerous nucleoside analog prodrugs routinely used in cancer and antiviral chemotherapy. For many of these compounds, the phosphorylation step catalyzed by dCK is the rate-limiting step in their overall activation pathway. To determine the factors that limit the phosphorylation efficiency of the prodrug, we solved the crystal structure of dCK to a resolution of 1.6 A in complex with its physiological substrate deoxycytidine and with the prodrugs AraC and gemcitabine. The structures reveal the determinants of dCK substrate specificity. Especially relevant to new prodrug development is the interaction between Arg128 and the hydrogen-bond acceptor at the sugar 2'-arabinosyl position of AraC and gemcitabine. On the basis of the structures, we designed a catalytically superior dCK variant that could be used in suicide gene-therapy applications.
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==Overview==
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Structure of human dCK suggests strategies to improve anticancer and antiviral therapy.,Sabini E, Ort S, Monnerjahn C, Konrad M, Lavie A Nat Struct Biol. 2003 Jul;10(7):513-9. PMID:12808445<ref>PMID:12808445</ref>
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Human deoxycytidine kinase (dCK) phosphorylates the natural, deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and, deoxyadenosine (dA) and is an essential enzyme for the phosphorylation of, numerous nucleoside analog prodrugs routinely used in cancer and antiviral, chemotherapy. For many of these compounds, the phosphorylation step, catalyzed by dCK is the rate-limiting step in their overall activation, pathway. To determine the factors that limit the phosphorylation, efficiency of the prodrug, we solved the crystal structure of dCK to a, resolution of 1.6 A in complex with its physiological substrate, deoxycytidine and with the prodrugs AraC and gemcitabine. The structures, reveal the determinants of dCK substrate specificity. Especially relevant, to new prodrug development is the interaction between Arg128 and the, hydrogen-bond acceptor at the sugar 2'-arabinosyl position of AraC and, gemcitabine. On the basis of the structures, we designed a catalytically, superior dCK variant that could be used in suicide gene-therapy, applications.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1P60 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ADP and DCZ as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Deoxycytidine_kinase Deoxycytidine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.74 2.7.1.74] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1P60 OCA].
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</div>
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<div class="pdbe-citations 1p60" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Structure of human dCK suggests strategies to improve anticancer and antiviral therapy., Sabini E, Ort S, Monnerjahn C, Konrad M, Lavie A, Nat Struct Biol. 2003 Jul;10(7):513-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12808445 12808445]
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*[[Deoxycytidine kinase|Deoxycytidine kinase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Deoxycytidine kinase]]
[[Category: Deoxycytidine kinase]]
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[[Category: Homo sapiens]]
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[[Category: Human]]
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[[Category: Single protein]]
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[[Category: Konrad, M]]
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[[Category: Konrad, M.]]
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[[Category: Lavie, A]]
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[[Category: Lavie, A.]]
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[[Category: Monnerjahn, C]]
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[[Category: Monnerjahn, C.]]
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[[Category: Ort, S]]
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[[Category: Ort, S.]]
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[[Category: Sabini, E]]
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[[Category: Sabini, E.]]
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[[Category: Deoxycytidine]]
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[[Category: ADP]]
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[[Category: Nucleoside kinase]]
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[[Category: DCZ]]
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[[Category: P-loop]]
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[[Category: deoxycytidine]]
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[[Category: Transferase]]
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[[Category: nucleoside kinase]]
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[[Category: p-loop]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:40:28 2007''
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Current revision

Structure of human dCK complexed with 2'-Deoxycytidine and ADP, Space group C 2 2 21

1p60, resolution 1.96Å

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