2zia

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{{Seed}}
 
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[[Image:2zia.png|left|200px]]
 
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==C4S dCK variant of dCK in complex with cladribine+UDP==
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The line below this paragraph, containing "STRUCTURE_2zia", creates the "Structure Box" on the page.
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<StructureSection load='2zia' size='340' side='right'caption='[[2zia]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2zia]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZIA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZIA FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 1.8&#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=CL9:2-CHLORO-2-DEOXYADENOSINE'>CL9</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene></td></tr>
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{{STRUCTURE_2zia| PDB=2zia | SCENE= }}
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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=2zia FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zia OCA], [https://pdbe.org/2zia PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zia RCSB], [https://www.ebi.ac.uk/pdbsum/2zia PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zia 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/zi/2zia_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=2zia 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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Purine nucleoside analogues of medicinal importance, such as cladribine, require phosphorylation by deoxycytidine kinase (dCK) for pharmacological activity. Structural studies of ternary complexes of human dCK show that the enzyme conformation adjusts to the different hydrogen-bonding properties between dA and dG and to the presence of substituent at the 2-position present in dG and cladribine. Specifically, the carbonyl group in dG elicits a previously unseen conformational adjustment of the active site residues Arg104 and Asp133. In addition, dG and cladribine adopt the anti conformation, in contrast to the syn conformation observed with dA. Kinetic analysis reveals that cladribine is phosphorylated at the highest efficiency with UTP as donor. We attribute this to the ability of cladribine to combine advantageous properties from dA (favorable hydrogen-bonding pattern) and dG (propensity to bind to the enzyme in its anti conformation), suggesting that dA analogues with a substituent at the 2-position are likely to be better activated by human dCK.
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===C4S dCK variant of dCK in complex with cladribine+UDP===
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Elucidation of Different Binding Modes of Purine Nucleosides to Human Deoxycytidine Kinase.,Sabini E, Hazra S, Konrad M, Lavie A J Med Chem. 2008 Jun 21;. PMID:18570408<ref>PMID:18570408</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2zia" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_18570408}}, adds the Publication Abstract to the page
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*[[ATPase 3D structures|ATPase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 18570408 is the PubMed ID number.
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*[[Deoxycytidine kinase 3D structures|Deoxycytidine kinase 3D structures]]
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== References ==
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{{ABSTRACT_PUBMED_18570408}}
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<references/>
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__TOC__
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==About this Structure==
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</StructureSection>
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2ZIA is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZIA OCA].
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==Reference==
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<ref group="xtra">PMID:18570408</ref><references group="xtra"/>
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[[Category: Deoxycytidine kinase]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Lavie, A.]]
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[[Category: Large Structures]]
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[[Category: Sabini, E.]]
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[[Category: Lavie A]]
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[[Category: 2-chloro-2'-deoxyadenosine]]
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[[Category: Sabini E]]
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[[Category: Atp-binding]]
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[[Category: Cladribine]]
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[[Category: Dck]]
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[[Category: Deoxyadenosine analog]]
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[[Category: Deoxycytidine kinase]]
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[[Category: Nucleoside]]
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[[Category: Nucleotide-binding]]
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[[Category: Nucleus]]
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[[Category: Phosphoprotein]]
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[[Category: Purine]]
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[[Category: Transferase]]
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[[Category: Udp]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 02:44:44 2009''
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Current revision

C4S dCK variant of dCK in complex with cladribine+UDP

PDB ID 2zia

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