1p62

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(New page: 200px<br /> <applet load="1p62" size="450" color="white" frame="true" align="right" spinBox="true" caption="1p62, resolution 1.90&Aring;" /> '''Structure of human ...)
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[[Image:1p62.gif|left|200px]]<br />
 
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<applet load="1p62" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1p62, resolution 1.90&Aring;" />
 
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'''Structure of human dCK complexed with gemcitabine and ADP-MG'''<br />
 
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==Overview==
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==Structure of human dCK complexed with gemcitabine and ADP-MG==
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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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<StructureSection load='1p62' size='340' side='right'caption='[[1p62]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1p62]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P62 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1P62 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=GEO:GEMCITABINE'>GEO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1p62 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p62 OCA], [https://pdbe.org/1p62 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1p62 RCSB], [https://www.ebi.ac.uk/pdbsum/1p62 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1p62 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://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/p6/1p62_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/main_output.php?pdb_ID=1p62 ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1P62 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with MG, ADP and GEO 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=1P62 OCA].
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*[[Deoxycytidine kinase 3D structures|Deoxycytidine kinase 3D structures]]
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== References ==
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==Reference==
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<references/>
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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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__TOC__
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[[Category: Deoxycytidine kinase]]
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
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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: ADP]]
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[[Category: GEO]]
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[[Category: MG]]
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[[Category: gemcitabine]]
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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 18:40:33 2007''
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Current revision

Structure of human dCK complexed with gemcitabine and ADP-MG

PDB ID 1p62

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