4ID5

HIV-1 reverse transcriptase with bound fragment at the RNase H primer grip site

Summary for 4ID5

• Entry DOI: 10.2210/pdb4id5/pdb
• Related: 4ICL 4IDK 4IFV 4IFY 4IG0 4IG3
• Descriptor: Reverse transcriptase/ribonuclease H, P51 RT, 4-{[4-({4-[(E)-2-cyanoethenyl]-2,6-dimethylphenyl}amino)pyrimidin-2-yl]amino}benzonitrile, ... (7 entities in total)
• Functional Keywords: rna-directed dna polymerase, dna polymerase, endonuclease, hydrolase, multifunctional enzyme, transferase-transferase inhibitor complex, transferase/transferase 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: 116006.97

Authors

Bauman, J.D.,Patel, D.,Arnold, E. (deposition date: 2012-12-11, release date: 2013-02-06, Last modification date: 2023-11-29)

Primary citation

Bauman, J.D.,Patel, D.,Dharia, C.,Fromer, M.W.,Ahmed, S.,Frenkel, Y.,Vijayan, R.S.,Eck, J.T.,Ho, W.C.,Das, K.,Shatkin, A.J.,Arnold, E.
Detecting Allosteric Sites of HIV-1 Reverse Transcriptase by X-ray Crystallographic Fragment Screening.
J.Med.Chem., 56:2738-2746, 2013

PubMed Abstract: HIV-1 reverse transcriptase (RT) undergoes a series of conformational changes during viral replication and is a central target for antiretroviral therapy. The intrinsic flexibility of RT can provide novel allosteric sites for inhibition. Crystals of RT that diffract X-rays to better than 2 Å resolution facilitated the probing of RT for new druggable sites using fragment screening by X-ray crystallography. A total of 775 fragments were grouped into 143 cocktails, which were soaked into crystals of RT in complex with the non-nucleoside drug rilpivirine (TMC278). Seven new sites were discovered, including the Incoming Nucleotide Binding, Knuckles, NNRTI Adjacent, and 399 sites, located in the polymerase region of RT, and the 428, RNase H Primer Grip Adjacent, and 507 sites, located in the RNase H region. Three of these sites (Knuckles, NNRTI Adjacent, and Incoming Nucleotide Binding) are inhibitory and provide opportunities for discovery of new anti-AIDS drugs.

PubMed: 23342998
DOI: 10.1021/jm301271j

Experimental method

X-RAY DIFFRACTION (1.95 Å)