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| | <StructureSection load='4c6a' size='340' side='right'caption='[[4c6a]], [[Resolution|resolution]] 1.25Å' scene=''> | | <StructureSection load='4c6a' size='340' side='right'caption='[[4c6a]], [[Resolution|resolution]] 1.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4c6a]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Dicdi Dicdi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C6A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4C6A FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4c6a]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Dictyostelium_discoideum Dictyostelium discoideum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C6A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4C6A FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Nucleoside-diphosphate_kinase Nucleoside-diphosphate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.6 2.7.4.6] </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=4c6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c6a OCA], [https://pdbe.org/4c6a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4c6a RCSB], [https://www.ebi.ac.uk/pdbsum/4c6a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4c6a ProSAT]</span></td></tr> |
| - | <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=4c6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c6a OCA], [http://pdbe.org/4c6a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4c6a RCSB], [http://www.ebi.ac.uk/pdbsum/4c6a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4c6a ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [[https://www.uniprot.org/uniprot/NDKC_DICDI NDKC_DICDI]] |
| - | The acyclic nucleosides thiophosphonates (9-[2-(thiophosphonomethoxy)ethyl]adenine (S-PMEA) and (R)-9-[2-(thiophosphonomethoxy)propyl]adenine (S-PMPA), exhibit antiviral activity against HIV-1, -2 and HBV. Their diphosphate forms S-PMEApp and S-PMPApp, synthesized as stereoisomeric mixture, are potent inhibitors of wild-type (WT) HIV-1 RT. Understanding HIV-1 RT stereoselectivity, however, awaits resolution of the diphosphate forms into defined stereoisomers. To this aim, thiophosphonate monophosphates S-PMEAp and S-PMPAp were synthesized and used in a stereocontrolled enzyme-catalyzed phosphoryl transfer reaction involving either nucleoside diphosphate kinase (NDPK) or creatine kinase (CK) to obtain thiophosphonate diphosphates as separated isomers. We then quantified substrate preference of recombinant WT HIV-1 RT toward pure stereoisomers using in vitro steady-state kinetic analyses. The crystal structure of a complex between Dictyostelium NDPK and S-PMPApp at 2.32A allowed to determine the absolute configuration at the alpha-phosphorus atom in relation to the stereo-preference of studied enzymes. The RP isomer of S-PMPApp and S-PMEApp are the preferred substrate over SP for both NDPK and HIV-1 RT.
| + | |
| - | | + | |
| - | Enzymatic synthesis of acyclic nucleoside thiophosphonate diphosphates: Effect of the alpha-phosphorus configuration on HIV-1 RT activity.,Priet S, Roux L, Saez-Ayala M, Ferron F, Canard B, Alvarez K Antiviral Res. 2015 Mar 9;117:122-131. doi: 10.1016/j.antiviral.2015.03.003. PMID:25766862<ref>PMID:25766862</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 4c6a" style="background-color:#fffaf0;"></div>
| + | |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Nucleoside diphosphate kinase|Nucleoside diphosphate kinase]] | + | *[[Nucleoside diphosphate kinase 3D structures|Nucleoside diphosphate kinase 3D structures]] |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Dicdi]] | + | [[Category: Dictyostelium discoideum]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Nucleoside-diphosphate kinase]]
| + | [[Category: Alvarez K]] |
| - | [[Category: Alvarez, K]] | + | [[Category: Canard B]] |
| - | [[Category: Canard, B]] | + | [[Category: Ferron F]] |
| - | [[Category: Ferron, F]] | + | [[Category: Priet S]] |
| - | [[Category: Priet, S]] | + | [[Category: Verron M]] |
| - | [[Category: Verron, M]] | + | |
| - | [[Category: Phosphotransferase]]
| + | |
| - | [[Category: Transferase]]
| + | |
