3LAK

Crystal structure of HIV-1 reverse transcriptase in complex with N1-heterocycle pyrimidinedione non-nucleoside inhibitor

3LAK の概要

• エントリーDOI: 10.2210/pdb3lak/pdb
• 関連するPDBエントリー: 3LAL 3LAM 3LAN
• 分子名称: HIV Reverse transcriptase, 3-({3-[(2-amino-6-fluoropyridin-4-yl)methyl]-5-(1-methylethyl)-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl}carbonyl)-5-methylbenzonitrile, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: hiv, reverse transcriptase, rt, nnrti, transferase
• 由来する生物種: Human immunodeficiency virus type 1 (HIV-1)
• 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
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 129967.03

構造登録者

Lansdon, E.B.,Mitchell, M.L. (登録日: 2010-01-06, 公開日: 2010-02-23, 最終更新日: 2023-09-06)

主引用文献

Mitchell, M.L.,Son, J.C.,Lee, I.Y.,Lee, C.K.,Kim, H.S.,Guo, H.,Wang, J.,Hayes, J.,Wang, M.,Paul, A.,Lansdon, E.B.,Chen, J.M.,Eisenberg, G.,Geleziunas, R.,Xu, L.,Kim, C.U.
N1-Heterocyclic pyrimidinediones as non-nucleoside inhibitors of HIV-1 reverse transcriptase.
Bioorg.Med.Chem.Lett., 20:1585-1588, 2010

PubMed Abstract: A series of N1-heterocyclic pyrimidinediones were extensively evaluated as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Inhibitor 1 is active against NNRTI-resistant viruses including RT mutant K103N. The co-crystal structure of inhibitor 1 with HIV-1 RT revealed that H-bonds are formed with K101 and K103. Efforts to improve the suboptimal pharmacokinetic profile of 1 resulted in the discovery of compound 13, which represents the lead compound in this series with improved pharmacokinetics and similar potency as inhibitor 1.

PubMed: 20137928
DOI: 10.1016/j.bmcl.2010.01.086

実験手法

X-RAY DIFFRACTION (2.3 Å)