7KRD

Crystal Structure of HIV-1 Reverse Transcriptase in Complex with 4-(3-chloro-5-cyanophenoxy)-3-(2-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)ethoxy)phenyl sulfurofluoridate (JLJ702)

7KRD の概要

• エントリーDOI: 10.2210/pdb7krd/pdb
• 分子名称: HIV-1 REVERSE TRANSCRIPTASE, P66 SUBUNIT, HIV-1 REVERSE TRANSCRIPTASE, P51 SUBUNIT, 4-(3-chloro-5-cyanophenoxy)-3-[2-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)ethoxy]phenyl sulfurofluoridate (3 entities in total)
• 機能のキーワード: polymerase, reverse transcriptase, non-nucleoside inhibitor, transferase, hydrolase-inhibitor complex, hydrolase/inhibitor
• 由来する生物種: Human immunodeficiency virus type 1 group M subtype B (isolate BH10); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 114510.57

構造登録者

Bertoletti, N.,Ippolito, J.A.,Jorgensen, W.L.,Anderson, K.S. (登録日: 2020-11-19, 公開日: 2021-01-13, 最終更新日: 2024-12-25)

主引用文献

Ippolito, J.A.,Niu, H.,Bertoletti, N.,Carter, Z.J.,Jin, S.,Spasov, K.A.,Cisneros, J.A.,Valhondo, M.,Cutrona, K.J.,Anderson, K.S.,Jorgensen, W.L.
Covalent Inhibition of Wild-Type HIV-1 Reverse Transcriptase Using a Fluorosulfate Warhead.
Acs Med.Chem.Lett., 12:249-255, 2021

PubMed Abstract: Covalent inhibitors of wild-type HIV-1 reverse transcriptase (CRTIs) are reported. Three compounds derived from catechol diether non-nucleoside inhibitors (NNRTIs) with addition of a fluorosulfate warhead are demonstrated to covalently modify Tyr181 of HIV-RT. X-ray crystal structures for complexes of the CRTIs with the enzyme are provided, which fully demonstrate the covalent attachment, and confirmation is provided by appropriate mass shifts in ESI-TOF mass spectra. The three CRTIs and six noncovalent analogues are found to be potent inhibitors with both IC values for in vitro inhibition of WT RT and EC values for cytopathic protection of HIV-1-infected human T-cells in the 5-320 nM range.

PubMed: 33603971
DOI: 10.1021/acsmedchemlett.0c00612

実験手法

X-RAY DIFFRACTION (2.7 Å)