3I8W

Crystal structure of a metallacarborane inhibitor bound to HIV protease

3I8W の概要

• エントリーDOI: 10.2210/pdb3i8w/pdb
• 関連するPDBエントリー: 1ZTZ
• 分子名称: Protease, COBALT BIS(1,2-DICARBOLLIDE), CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: inhibitor, cobalt bis(1, 2-dicarbollide), viral resistance, aspartic protease, aids, aspartyl protease, capsid maturation, capsid protein, cell membrane, 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-finger, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Human immunodeficiency virus type 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): P03367
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11256.10

構造登録者

Rezacova, P. (登録日: 2009-07-10, 公開日: 2009-12-01, 最終更新日: 2023-09-06)

主引用文献

Pokorna, J.,Brynda, J.,Cigler, P.,Fanfrlik, J.,Sieglova, I.,Oberwinkler, H.,Hobza, P.,Kral, V.,Konvalinka, J.
Design of HIV Protease Inhibitors Based on Inorganic Polyhedral Metallacarboranes
J.Med.Chem., 52:7132-7141, 2009

PubMed Abstract: HIV protease (HIV PR) is a primary target for anti-HIV drug design. We have previously identified and characterized substituted metallacarboranes as a new class of HIV protease inhibitors. In a structure-guided drug design effort, we connected the two cobalt bis(dicarbollide) clusters with a linker to substituted ammonium group and obtained a set of compounds based on a lead formula [H(2)N-(8-(C(2)H(4)O)(2)-1,2-C(2)B(9)H(10))(1',2'-C(2)B(9)H(11))-3,3'-Co)(2)]Na. We explored inhibition properties of these compounds with various substitutions, determined the HIV PR:inhibitor crystal structure, and computationally explored the conformational space of the linker. Our results prove the capacity of linker-substituted dual-cage cobalt bis(dicarbollides) as lead compounds for design of more potent inhibitors of HIV PR.

PubMed: 19874035
DOI: 10.1021/jm9011388

実験手法

X-RAY DIFFRACTION (1.7 Å)