4cp5: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4cp5]] is a 6 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=4CP5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CP5 FirstGlance]. <br> | <table><tr><td colspan='2'>[[4cp5]] is a 6 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=4CP5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CP5 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.32Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4cp5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cp5 OCA], [https://pdbe.org/4cp5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cp5 RCSB], [https://www.ebi.ac.uk/pdbsum/4cp5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cp5 ProSAT]</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=4cp5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cp5 OCA], [https://pdbe.org/4cp5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cp5 RCSB], [https://www.ebi.ac.uk/pdbsum/4cp5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cp5 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/NDKC_DICDI NDKC_DICDI] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
Latest revision as of 15:14, 20 December 2023
ndpK in complex with (Rp)-SPMPAppndpK in complex with (Rp)-SPMPApp
Structural highlights
FunctionPublication 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. See AlsoReferences
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