View source for 5mqj


==Crystal structure of dCK mutant C3S==
<StructureSection load='5mqj' size='340' side='right'caption='[[5mqj]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5mqj]] is a 4 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=5MQJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MQJ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5mqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mqj OCA], [https://pdbe.org/5mqj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mqj RCSB], [https://www.ebi.ac.uk/pdbsum/5mqj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mqj ProSAT]</span></td></tr>
</table>
== Function ==
[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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Masitinib, a highly selective protein kinase inhibitor, can sensitise gemcitabine-refractory cancer cell lines when used in combination with gemcitabine. Here we report a reverse proteomic approach that identifies the target responsible for this sensitisation: the deoxycytidine kinase (dCK). Masitinib, as well as other protein kinase inhibitors, such as imatinib, interact with dCK and provoke an unforeseen conformational-dependent activation of this nucleoside kinase, modulating phosphorylation of nucleoside analogue drugs. This phenomenon leads to an increase of prodrug phosphorylation of most of the chemotherapeutic drugs activated by this nucleoside kinase. The unforeseen dual activity of protein kinase inhibition/nucleoside kinase activation could be of great therapeutic benefit, through either reducing toxicity of therapeutic agents by maintaining effectiveness at lower doses or by counteracting drug resistance initiated via down modulation of dCK target.

Dual protein kinase and nucleoside kinase modulators for rationally designed polypharmacology.,Hammam K, Saez-Ayala M, Rebuffet E, Gros L, Lopez S, Hajem B, Humbert M, Baudelet E, Audebert S, Betzi S, Lugari A, Combes S, Letard S, Casteran N, Mansfield C, Moussy A, De Sepulveda P, Morelli X, Dubreuil P Nat Commun. 2017 Nov 10;8(1):1420. doi: 10.1038/s41467-017-01582-5. PMID:29127277<ref>PMID:29127277</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5mqj" style="background-color:#fffaf0;"></div>

==See Also==
*[[Deoxycytidine kinase 3D structures|Deoxycytidine kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Audebert S]]
[[Category: Baudelet E]]
[[Category: Betzi S]]
[[Category: Combes S]]
[[Category: Dubreuil P]]
[[Category: Gros L]]
[[Category: Hajem B]]
[[Category: Hammam K]]
[[Category: Humbert M]]
[[Category: Letard S]]
[[Category: Lopez S]]
[[Category: Lugari A]]
[[Category: Mansfield C]]
[[Category: Morelli X]]
[[Category: Moussy A]]
[[Category: Pez D]]
[[Category: Rebuffet E]]
[[Category: Saez-Ayala M]]
[[Category: De Sepulveda P]]