2no6
From Proteopedia
(Difference between revisions)
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==C4S dCK variant of dCK in complex with FTC+ADP== | ==C4S dCK variant of dCK in complex with FTC+ADP== | ||
| - | <StructureSection load='2no6' size='340' side='right'caption='[[2no6]]' scene=''> | + | <StructureSection load='2no6' size='340' side='right'caption='[[2no6]], [[Resolution|resolution]] 1.90Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NO6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NO6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2no6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NO6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NO6 FirstGlance]. <br> |
| - | </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=2no6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2no6 OCA], [https://pdbe.org/2no6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2no6 RCSB], [https://www.ebi.ac.uk/pdbsum/2no6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2no6 ProSAT]</span></td></tr> | + | </td></tr><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=ETV:4-AMINO-5-FLUORO-1-[(2R,5S)-2-(HYDROXYMETHYL)-1,3-OXATHIOLAN-5-YL]PYRIMIDIN-2(1H)-ONE'>ETV</scene></td></tr> |
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1p5z|1p5z]], [[1p60|1p60]], [[1p61|1p61]], [[1p62|1p62]], [[2a2z|2a2z]], [[2a30|2a30]], [[2no0|2no0]], [[2no1|2no1]], [[1no7|1no7]], [[2no9|2no9]], [[2noa|2noa]]</div></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DCK ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Deoxycytidine_kinase Deoxycytidine kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.74 2.7.1.74] </span></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=2no6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2no6 OCA], [https://pdbe.org/2no6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2no6 RCSB], [https://www.ebi.ac.uk/pdbsum/2no6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2no6 ProSAT]</span></td></tr> | ||
</table> | </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> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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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=2no6 ConSurf]. | </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=2no6 ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Biological molecules are predominantly enantioselective. Yet currently two nucleoside analogue prodrugs (3TC and FTC) with opposite chirality compared to physiological nucleosides are clinically approved for the treatment of HIV infections. These prodrugs require conversion to their triphosphorylated forms to achieve pharmacological activity. The first step in the activation of these agents is catalyzed by human deoxycytidine kinase (dCK). This enzyme possesses the ability to phosphorylate nucleosides of the unnatural l-chirality. To understand the molecular basis for the nonenantioselectivity of dCK, we solved the crystal structures of the enzyme in complex with the l-enantiomer and of its physiological substrate deoxycytidine and with the l-nucleoside analogue FTC. These were compared to a structure solved with d-dC. Our results highlight structural adjustments imposed on the l-nucleosides and properties of the enzyme endowing it with the ability to phosphorylate substrates with nonphysiological chirality. This work reveals the molecular basis for the activation of l-nucleosides by dCK. | ||
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| + | Nonenantioselectivity Property of Human Deoxycytidine Kinase Explained by Structures of the Enzyme in Complex with l- and d-Nucleosides.,Sabini E, Hazra S, Konrad M, Lavie A J Med Chem. 2007 Jun 28;50(13):3004-14. Epub 2007 May 27. PMID:17530837<ref>PMID:17530837</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 2no6" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Deoxycytidine kinase 3D structures|Deoxycytidine kinase 3D structures]] | *[[Deoxycytidine kinase 3D structures|Deoxycytidine kinase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Deoxycytidine kinase]] | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Burley | + | [[Category: Burley, S K]] |
| - | [[Category: Hazra S]] | + | [[Category: Hazra, S]] |
| - | [[Category: Konrad M]] | + | [[Category: Konrad, M]] |
| - | [[Category: Lavie A]] | + | [[Category: Lavie, A]] |
| - | [[Category: Sabini E]] | + | [[Category: Sabini, E]] |
| + | [[Category: Antiviral]] | ||
| + | [[Category: Dck]] | ||
| + | [[Category: Emtricitabine]] | ||
| + | [[Category: Enantiomer]] | ||
| + | [[Category: Ftc]] | ||
| + | [[Category: Human deoxycytidine kinase]] | ||
| + | [[Category: Transferase]] | ||
Revision as of 18:06, 20 October 2021
C4S dCK variant of dCK in complex with FTC+ADP
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Categories: Deoxycytidine kinase | Human | Large Structures | Burley, S K | Hazra, S | Konrad, M | Lavie, A | Sabini, E | Antiviral | Dck | Emtricitabine | Enantiomer | Ftc | Human deoxycytidine kinase | Transferase
