2WOM

Crystal Structure of UK-453061 bound to HIV-1 Reverse Transcriptase (K103N).

2WOM の概要

• エントリーDOI: 10.2210/pdb2wom/pdb
• 関連するPDBエントリー: 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 3PHV
• 分子名称: HIV-1 REVERSE TRANSCRIPTASE, 5-{[3,5-diethyl-1-(2-hydroxyethyl)-1H-pyrazol-4-yl]oxy}benzene-1,3-dicarbonitrile (3 entities in total)
• 機能のキーワード: aids, non-nucleoside inhibitor, drug design, transferase, nnrti, sbdd
• 由来する生物種: HUMAN IMMUNODEFICIENCY VIRUS 1; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 116242.19

構造登録者

Phillips, C.,Irving, S.L.,Knoechel, T.,Ringrose, H. (登録日: 2009-07-27, 公開日: 2010-08-11, 最終更新日: 2023-12-20)

主引用文献

Corbau, R.,Mori, J.,Phillips, C.,Fishburn, L.,Martin, A.,Mowbray, C.,Panton, W.,Smith-Burchnell, C.,Thornberry, A.,Ringrose, H.,Knochel, T.,Irving, S.,Westby, M.,Wood, A.,Perros, M.
Lersivirine, a nonnucleoside reverse transcriptase inhibitor with activity against drug-resistant human immunodeficiency virus type 1.
Antimicrob. Agents Chemother., 54:4451-4463, 2010

PubMed Abstract: The nonnucleoside reverse transcriptase inhibitors (NNRTIs) are key components of highly active antiretroviral therapy (HAART) for the treatment of human immunodeficiency virus type 1 (HIV-1). A major problem with the first approved NNRTIs was the emergence of mutations in the HIV-1 reverse transcriptase (RT), in particular K103N and Y181C, which led to resistance to the entire class. We adopted an iterative strategy to synthesize and test small molecule inhibitors from a chemical series of pyrazoles against wild-type (wt) RT and the most prevalent NNRTI-resistant mutants. The emerging candidate, lersivirine (UK-453,061), binds the RT enzyme in a novel way (resulting in a unique resistance profile), inhibits over 60% of viruses bearing key RT mutations, with 50% effective concentrations (EC(50)s) within 10-fold of those for wt viruses, and has excellent selectivity against a range of human targets. Altogether lersivirine is a highly potent and selective NNRTI, with excellent efficacy against NNRTI-resistant viruses.

PubMed: 20660667
DOI: 10.1128/AAC.01455-09

実験手法

X-RAY DIFFRACTION (3.2 Å)