3qeo

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==S74E-R104M-D133A dCK variant in complex with L-deoxythymidine and UDP==
==S74E-R104M-D133A dCK variant in complex with L-deoxythymidine and UDP==
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<StructureSection load='3qeo' size='340' side='right' caption='[[3qeo]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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<StructureSection load='3qeo' size='340' side='right'caption='[[3qeo]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3qeo]] is a 2 chain structure with sequence 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=3QEO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QEO FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3qeo]] 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=3QEO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QEO 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=LLT:L-DEOXYTHYMIDINE'>LLT</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene></td></tr>
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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]] 1.897&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3qej|3qej]], [[3qen|3qen]]</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=LLT:L-DEOXYTHYMIDINE'>LLT</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene></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 Homo sapiens])</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=3qeo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qeo OCA], [https://pdbe.org/3qeo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qeo RCSB], [https://www.ebi.ac.uk/pdbsum/3qeo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qeo ProSAT]</span></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=3qeo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qeo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qeo RCSB], [http://www.ebi.ac.uk/pdbsum/3qeo PDBsum]</span></td></tr>
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</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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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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Deoxycytidine kinase (dCK) uses either ATP or UTP as phosphoryl donors to catalyze the phosphorylation of nucleoside acceptors. The kinetic properties of human dCK are modulated in vivo by phosphorylation of serine 74. This residue is a part of the insert region and is situated distant to the active site. Replacing the serine with a glutamic acid (S74E variant) can mimic phosphorylation of Ser74. To understand how phosphorylation affects the catalytic properties of dCK, we examined the S74E variant of dCK both structurally and kinetically. We observe that the presence of a glutamic acid at position 74 favors the enzyme adopting the open conformation. Glu74 stabilizes the open conformation by directly interacting with the indole side chain of Trp58, a residue that is in close proximity to the base of the nucleoside substrate. The open dCK conformation is competent for the binding of nucleoside but not for phosphoryl transfer. In contrast, the closed conformation is competent for phosphoryl transfer but not for product release. Thus, dCK must transition between the open and closed states during the catalytic cycle. We propose a reaction scheme for dCK that incorporates the transition between the open and closed states, and this serves to rationalize the observed kinetic differences between wild type dCK and the S74E variant.
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Post-translational phosphorylation of serine 74 of human deoxycytidine kinase favors the enzyme adopting the open conformation making it competent for nucleoside binding and release.,Hazra S, Szewczak A, Ort S, Konrad M, Lavie A Biochemistry. 2011 Feb 25. PMID:21351740<ref>PMID:21351740</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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==See Also==
==See Also==
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*[[Deoxycytidine kinase|Deoxycytidine kinase]]
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*[[Deoxycytidine kinase 3D structures|Deoxycytidine kinase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Deoxycytidine kinase]]
 
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Hazra, S]]
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[[Category: Large Structures]]
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[[Category: Lavie, A]]
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[[Category: Hazra S]]
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[[Category: Alpha/beta]]
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[[Category: Lavie A]]
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[[Category: Phosphoryl transfer]]
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[[Category: Transferase]]
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Current revision

S74E-R104M-D133A dCK variant in complex with L-deoxythymidine and UDP

PDB ID 3qeo

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