1PWU

Crystal Structure of Anthrax Lethal Factor complexed with (3-(N-hydroxycarboxamido)-2-isobutylpropanoyl-Trp-methylamide), a known small molecule inhibitor of matrix metalloproteases.

1PWU の概要

• エントリーDOI: 10.2210/pdb1pwu/pdb
• 関連するPDBエントリー: 1PQW 1PWP 1PWV 1PWW
• 分子名称: Lethal factor, ZINC ION, 3-(N-HYDROXYCARBOXAMIDO)-2-ISOBUTYLPROPANOYL-TRP-METHYLAMIDE (3 entities in total)
• 機能のキーワード: anthrax toxin, lethal factor, small molecule peptidic inhibitor, hydroxamic acid., hydrolase
• 由来する生物種: Bacillus anthracis
• 細胞内の位置: Secreted: P15917
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 181569.41

構造登録者

Wong, T.Y.,Schwarzenbacher, R.,Liddington, R.C. (登録日: 2003-07-02, 公開日: 2004-02-03, 最終更新日: 2023-08-16)

主引用文献

Turk, B.E.,Wong, T.Y.,Schwarzenbacher, R.,Jarrell, E.T.,Leppla, S.H.,Collier, R.J.,Liddington, R.C.,Cantley, L.C.
The structural basis for substrate and inhibitor selectivity of the anthrax lethal factor.
Nat.Struct.Mol.Biol., 11:60-66, 2004

PubMed Abstract: Recent events have created an urgent need for new therapeutic strategies to treat anthrax. We have applied a mixture-based peptide library approach to rapidly determine the optimal peptide substrate for the anthrax lethal factor (LF), a metalloproteinase with an important role in the pathogenesis of the disease. Using this approach we have identified peptide analogs that inhibit the enzyme in vitro and that protect cultured macrophages from LF-mediated cytolysis. The crystal structures of LF bound to an optimized peptide substrate and to peptide-based inhibitors provide a rationale for the observed selectivity and may be exploited in the design of future generations of LF inhibitors.

PubMed: 14718924
DOI: 10.1038/nsmb708

実験手法

X-RAY DIFFRACTION (2.7 Å)