2YNF

HIV-1 Reverse Transcriptase Y188L mutant in complex with inhibitor GSK560

Summary for 2YNF

• Entry DOI: 10.2210/pdb2ynf/pdb
• Related: 1A30 1BV7 1BV9 1BVE 1BVG 1BWA 1BWB 1C0T 1C0U 1C1B 1C1C 1DMP 1DTQ 1DTT 1E6J 1EP4 1ESK 1EX4 1EXQ 1FB7 1FK9 1FKO 1FKP 1G6L 1HIV 1HVH 1HVR 1HWR 1HXB 1JKH 1JLA 1JLB 1JLC 1JLE 1JLF 1JLG 1JLQ 1KLM 1LV1 1LW0 1LW2 1LWC 1LWE 1LWF 1NCP 1O1W 1ODW 1ODY 1QBR 1QBS 1QBT 1QBU 1REV 1RT1 1RT2 1RT3 1RT4 1RT5 1RT6 1RT7 1RTD 1RTH 1RTI 1RTJ 1S1T 1S1U 1S1V 1S1W 1S1X 1T05 1TAM 1TKT 1TKX 1TKZ 1TL1 1TL3 1VRT 1VRU 2WHH 2WOM 2WON 2YNG 2YNH 2YNI 3PHV 4B3O 4B3P 4B3Q
• Descriptor: REVERSE TRANSCRIPTASE/RIBONUCLEASE H, P51 RT, MAGNESIUM ION, ... (6 entities in total)
• Functional Keywords: hydrolase, nnrti
• Biological source: HIV-1 M\:B_HXB2R (HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 (HXB2 ISOLATE)); 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: 117806.30

Authors

Chong, P.,Sebahar, P.,Youngman, M.,Garrido, D.,Zhang, H.,Stewart, E.L.,Nolte, R.T.,Wang, L.,Ferris, R.G.,Edelstein, M.,Weaver, K.,Mathis, A.,Peat, A. (deposition date: 2012-10-14, release date: 2013-01-09, Last modification date: 2023-12-20)

Primary citation

Chong, P.,Sebahar, P.,Youngman, M.,Garrido, D.,Zhang, H.,Stewart, E.L.,Nolte, R.T.,Wang, L.,Ferris, R.G.,Edelstein, M.,Weaver, K.,Mathis, A.,Peat, A.
Rational Design of Potent Non-Nucleoside Inhibitors of HIV-1 Reverse Transcriptase.
J.Med.Chem., 55:10601-, 2012

PubMed Abstract: A new series of non-nucleoside reverse transcriptase inhibitors based on an imidazole-amide biarylether scaffold has been identified and shown to possess potent antiviral activity against HIV-1, including the NNRTI-resistant Y188L mutated virus. X-ray crystallography of inhibitors bound to reverse transcriptase, including a structure of the Y188L RT protein, was used extensively to help identify and optimize the key hydrogen-bonding motif. This led directly to the design of compound 43 that exhibits remarkable antiviral activity (EC50<1 nM) against a wide range of NNRTI-resistant viruses and a favorable pharmacokinetic profile across multiple species.

PubMed: 23137340
DOI: 10.1021/JM301294G

Experimental method

X-RAY DIFFRACTION (2.36 Å)