3BGC

HIV-1 protease in complex with a benzyl decorated oligoamine

3BGC の概要

• エントリーDOI: 10.2210/pdb3bgc/pdb
• 関連するPDBエントリー: 3BGB
• 分子名称: Protease, N,N'-(iminodiethane-2,1-diyl)bis(4-amino-N-benzylbenzenesulfonamide), CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: protein-ligand complex, aids, aspartyl protease, capsid maturation, core protein, cytoplasm, dna integration, dna recombination, dna-directed dna polymerase, endonuclease, hydrolase, lipoprotein, magnesium, membrane, metal-binding, multifunctional enzyme, myristate, nuclease, nucleotidyltransferase, nucleus, phosphoprotein, protease, rna-binding, rna-directed dna polymerase, transferase, viral nucleoprotein, virion, zinc, zinc-finger
• 由来する生物種: Human immunodeficiency virus type 1 (Viruses)
• 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): P03367
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22272.18

構造登録者

Boettcher, J.,Blum, A.,Sammet, B.,Heine, A.,Diederich, W.E.,Klebe, G. (登録日: 2007-11-26, 公開日: 2008-09-02, 最終更新日: 2023-11-01)

主引用文献

Blum, A.,Sammet, B.,Luksch, T.,Heine, A.,Klebe, G.,Diederich, W.E.
Achiral oligoamines as versatile tool for the development of aspartic protease inhibitors
Bioorg.Med.Chem., 16:8574-8586, 2008

PubMed Abstract: Due to the important role that aspartic proteases play in many patho-physiological processes, they have intensively been targeted by modern drug development. However, up to now, only for two family members, renin and HIV protease, approved drugs are available. Inhibitor development, mostly guided by mimicking the natural peptide substrates, resulted in very potent inhibitors for several targets, but the pharmacokinetic properties of these compounds were often not optimal. Herein we report a novel approach for lead structure discovery of non-peptidic aspartic protease inhibitors using easily accessible achiral linear oligoamines as starting point. An initial library comprising 11 inhibitors was developed and screened against six selected aspartic proteases. Several hits could be identified, among them selective as well as rather promiscuous inhibitors. The design concept was confirmed by determination of the crystal structure of two derivatives in complex with the HIV-1 protease, and represents a promising basis for the further inhibitor development.

PubMed: 18760609
DOI: 10.1016/j.bmc.2008.08.012

実験手法

X-RAY DIFFRACTION (1.8 Å)