4cp5: Difference between revisions
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==ndpK in complex with (Rp)-SPMPApp== | ==ndpK in complex with (Rp)-SPMPApp== | ||
<StructureSection load='4cp5' size='340' side='right' caption='[[4cp5]], [[Resolution|resolution]] 2.32Å' scene=''> | <StructureSection load='4cp5' size='340' side='right' caption='[[4cp5]], [[Resolution|resolution]] 2.32Å' scene=''> | ||
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EOI:[[(2R)-1-(6-AMINOPURIN-9-YL)PROPAN-2-YL]OXYMETHYL-SULFANYL-PHOSPHORYL]+PHOSPHONO+HYDROGEN+PHOSPHATE'>EOI</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EOI:[[(2R)-1-(6-AMINOPURIN-9-YL)PROPAN-2-YL]OXYMETHYL-SULFANYL-PHOSPHORYL]+PHOSPHONO+HYDROGEN+PHOSPHATE'>EOI</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='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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4cp5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cp5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4cp5 RCSB], [http://www.ebi.ac.uk/pdbsum/4cp5 PDBsum]</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=4cp5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cp5 OCA], [http://pdbe.org/4cp5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cp5 RCSB], [http://www.ebi.ac.uk/pdbsum/4cp5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cp5 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4cp5" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 03:07, 26 January 2017
ndpK in complex with (Rp)-SPMPAppndpK in complex with (Rp)-SPMPApp
Structural highlights
Publication Abstract from PubMedThe 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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