title: A comparison of the conformations of the 5'-triphosphates of zidovudine (AZT) and thymidine bound to HIV-1 reverse transcriptase.
abstract: Nuclear Overhauser effect experiments were performed at 500 MHz to determine the conformations of AZTTP and dTTP when bound to HIV-1 reverse transcriptase. The conformations of both ligands were found to be similar in the bound state. The orientation of the glycosidic angle is anti (chi = -120 degrees +/- 12 for AZTTP and -110 degrees +/- 12 for dTTP), gamma is +sc and the pucker of the 3'-azido-2',3'-dideoxy- and 2'-deoxyribose rings is predominantly C4' exo (P = 60 degrees +/- 10 for AZTTP and 55 degrees +/- 8 for dTTP). These results indicate that the unusual C4'endo/C3'exo pucker (P = 215 degrees) reported for the dideoxyribose ring of AZT in the solid state does not play a role in the interaction of HIV-1 reverse transcriptase with AZTTP.
authors.affiliation: Division of Virology, Burroughs Wellcome Co., Research Triangle Park, NC 27709.
authors.forename: G R
authors.initials: GR
authors.lastname: Painter
authors.forename: A E
authors.initials: AE
authors.lastname: Aulabaugh
authors.forename: C W
authors.initials: CW
authors.lastname: Andrews
mesh_terms: D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000201:enzymology*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011485:Protein Binding; D012194:RNA-Directed DNA Polymerase / Q000648:ultrastructure*; D011994:Recombinant Proteins / Q000648:ultrastructure; D013936:Thymidine / Q000737:chemistry*; D015215:Zidovudine / Q000737:chemistry*
chemical_list: D011994:Recombinant Proteins; D015215:Zidovudine; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase; D013936:Thymidine