3BC4

I84V HIV-1 protease in complex with a pyrrolidine diester

3BC4 の概要

• エントリーDOI: 10.2210/pdb3bc4/pdb
• 分子名称: protease, 2-aminoethyl naphthalen-1-ylacetate, DIMETHYL SULFOXIDE, ... (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: 1
• 化学式量合計: 11326.41

構造登録者

Boettcher, J.,Blum, A.,Heine, A.,Diederich, W.E.,Klebe, G. (登録日: 2007-11-12, 公開日: 2008-09-02, 最終更新日: 2023-11-01)

主引用文献

Blum, A.,Heine, A.,Diederich, W.E.,Klebe, G.
Targeting the open-flap conformation of HIV-1 protease with pyrrolidine-based inhibitors
Chemmedchem, 3:1337-1344, 2008

PubMed Abstract: HIV protease is a well-established drug target in antiviral chemotherapy. Immense research efforts have been made to discover effective inhibitors, thus making the enzyme one of the most studied and best characterized proteins. Although the protease exhibits high flexibility, all approved drugs target virtually the same protein conformation. The development of viral cross-resistance demands the generation of inhibitors with novel scaffolds and deviating modes of binding. Herein we report the design and the short, high-yielding stereoselective synthesis of a series of chiral, symmetric pyrrolidine-based inhibitors targeting the open-flap conformation of the protease. The obtained co-crystal structure with one derivative provides a valuable starting point for further inhibitor design.

PubMed: 18720485
DOI: 10.1002/cmdc.200800113

実験手法

X-RAY DIFFRACTION (1.82 Å)