3QIP

Structure of HIV-1 reverse transcriptase in complex with an RNase H inhibitor and nevirapine

Summary for 3QIP

• Entry DOI: 10.2210/pdb3qip/pdb
• Descriptor: Reverse HIV-1 reverse transcriptase p66, p51, 11-CYCLOPROPYL-5,11-DIHYDRO-4-METHYL-6H-DIPYRIDO[3,2-B:2',3'-E][1,4]DIAZEPIN-6-ONE, ... (8 entities in total)
• Functional Keywords: hiv, reverse transcriptase, rnase h, polymerase, nuclease, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: HIV-1 M:B_HXB2R (HIV-1); More
• Cellular location: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P04585 P04585
• Total number of polymer chains: 2
• Total formula weight: 116962.55

Authors

Lansdon, E.B.,Kirschberg, T.A. (deposition date: 2011-01-27, release date: 2011-04-20, Last modification date: 2023-09-13)

Primary citation

Lansdon, E.B.,Liu, Q.,Leavitt, S.A.,Balakrishnan, M.,Perry, J.K.,Lancaster-Moyer, C.,Kutty, N.,Liu, X.,Squires, N.H.,Watkins, W.J.,Kirschberg, T.A.
Structural and Binding Analysis of Pyrimidinol Carboxylic Acid and N-Hydroxy Quinazolinedione HIV-1 RNase H Inhibitors.
Antimicrob.Agents Chemother., 55:2905-2915, 2011

PubMed Abstract: HIV-1 RNase H breaks down the intermediate RNA-DNA hybrids during reverse transcription, requiring two divalent metal ions for activity. Pyrimidinol carboxylic acid and N-hydroxy quinazolinedione inhibitors were designed to coordinate the two metal ions in the active site of RNase H. High-resolution (1.4 Å to 2.1 Å) crystal structures were determined with the isolated RNase H domain and reverse transcriptase (RT), which permit accurate assessment of the metal and water environment at the active site. The geometry of the metal coordination suggests that the inhibitors mimic a substrate state prior to phosphodiester catalysis. Surface plasmon resonance studies confirm metal-dependent binding to RNase H and demonstrate that the inhibitors do not bind at the polymerase active site of RT. Additional evaluation of the RNase H site reveals an open protein surface with few additional interactions to optimize active-site inhibitors.

PubMed: 21464257
DOI: 10.1128/AAC.01594-10

Experimental method

X-RAY DIFFRACTION (2.0926 Å)