4c6a

High Resolution Structure of the Nucleoside diphosphate kinase

spinqualitylabelsall models 4c6a, resolution 1.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4c6a is a 1 chain structure with sequence from Dictyostelium discoideum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.25Å Ligands: PEG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NDKC_DICDI Publication Abstract from PubMed 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Nucleoside diphosphate kinase 3D structures

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