4H4M

Crystal Structure of HIV-1 Reverse Transcriptase in Complex with (E)-3-(3-chloro-5-(4-chloro-2-(2-(2,4-dioxo-3,4- dihydropyrimidin-1(2H)-yl)ethoxy)phenoxy)phenyl)acrylonitrile (JLJ494), a Non-nucleoside Inhibitor

Summary for 4H4M

• Entry DOI: 10.2210/pdb4h4m/pdb
• Related: 1S9E 2BE2 2ZD1 4H4O
• Descriptor: Reverse transcriptase/ribonuclease H, Exoribonuclease H, p66 RT, Reverse transcriptase/ribonuclease H, Exoribonuclease H, p51 RT, (2E)-3-(3-chloro-5-{4-chloro-2-[2-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)ethoxy]phenoxy}phenyl)prop-2-enenitrile, ... (5 entities in total)
• Functional Keywords: polymerase, transferase, hydrolase/inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Human immunodeficiency virus type 1 (HIV-1); More
• Cellular location: Gag-Pol polyprotein: Host cell membrane; Lipid-anchor. Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P03366 P03366
• Total number of polymer chains: 2
• Total formula weight: 114535.06

Authors

Frey, K.M.,Anderson, K.S. (deposition date: 2012-09-17, release date: 2012-12-05, Last modification date: 2023-09-20)

Primary citation

Frey, K.M.,Bollini, M.,Mislak, A.C.,Cisneros, J.A.,Gallardo-Macias, R.,Jorgensen, W.L.,Anderson, K.S.
Crystal Structures of HIV-1 Reverse Transcriptase with Picomolar Inhibitors Reveal Key Interactions for Drug Design.
J.Am.Chem.Soc., 134:19501-19503, 2012

PubMed Abstract: X-ray crystal structures at 2.9 Å resolution are reported for two complexes of catechol diethers with HIV-1 reverse transcriptase. The results help elucidate the structural origins of the extreme antiviral activity of the compounds. The possibility of halogen bonding between the inhibitors and Pro95 is addressed. Structural analysis reveals key interactions with conserved residues P95 and W229 of importance for design of inhibitors with high potency and favorable resistance profiles.

PubMed: 23163887
DOI: 10.1021/ja3092642

Experimental method

X-RAY DIFFRACTION (2.85 Å)