3E01

HIV-RT with non-nucleoside inhibitor annulated pyrazole 2

3E01 の概要

• エントリーDOI: 10.2210/pdb3e01/pdb
• 関連するPDBエントリー: 3DYA
• 分子名称: Gag-Pol polyprotein, 3-[2-bromo-4-(1H-pyrazolo[3,4-c]pyridazin-3-ylmethyl)phenoxy]-5-methylbenzonitrile (3 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: Human immunodeficiency virus type 1 (HIV-1); 詳細
• 細胞内の位置: 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
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 116529.43

構造登録者

Harris, S.F.,Villasenor, A. (登録日: 2008-07-30, 公開日: 2008-11-25, 最終更新日: 2024-02-21)

主引用文献

Sweeney, Z.K.,Harris, S.F.,Arora, S.F.,Javanbakht, H.,Li, Y.,Fretland, J.,Davidson, J.P.,Billedeau, J.R.,Gleason, S.K.,Hirschfeld, D.,Kennedy-Smith, J.J.,Mirzadegan, T.,Roetz, R.,Smith, M.,Sperry, S.,Suh, J.M.,Wu, J.,Tsing, S.,Villasenor, A.G.,Paul, A.,Su, G.,Heilek, G.,Hang, J.Q.,Zhou, A.S.,Jernelius, J.A.,Zhang, F.J.,Klumpp, K.
Design of annulated pyrazoles as inhibitors of HIV-1 reverse transcriptase
J.Med.Chem., 51:7449-7458, 2008

PubMed Abstract: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are recommended components of preferred combination antiretroviral therapies used for the treatment of HIV. These regimens are extremely effective in suppressing virus replication. Structure-based optimization of diaryl ether inhibitors led to the discovery of a new series of pyrazolo[3,4-c]pyridazine NNRTIs that bind the reverse transcriptase enzyme of human immunodeficiency virus-1 (HIV-RT) in an expanded volume relative to most other inhibitors in this class.The binding mode maintains the beta13 and beta14 strands bearing Pro236 in a position similar to that in the unliganded reverse transcriptase structure, and the distribution of interactions creates the opportunity for substantial resilience to single point mutations. Several pyrazolopyridazine NNRTIs were found to be highly effective against wild-type and NNRTI-resistant viral strains in cell culture.

PubMed: 19007201
DOI: 10.1021/jm800527x

実験手法

X-RAY DIFFRACTION (2.95 Å)