3BC3

Exploring inhibitor binding at the S subsites of cathepsin L

3BC3 の概要

• エントリーDOI: 10.2210/pdb3bc3/pdb
• 関連するPDBエントリー: 1MHW
• 分子名称: Cathepsin L heavy and light chains, S-benzyl-N-(biphenyl-4-ylacetyl)-L-cysteinyl-N~5~-(diaminomethyl)-D-ornithyl-N-(2-phenylethyl)-L-tyrosinamide (3 entities in total)
• 機能のキーワード: cathepsin l inhibitor binding at the s subsites, glycoprotein, hydrolase, lysosome, protease, thiol protease, zymogen
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Lysosome: P07711
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 50107.50

構造登録者

Chowdhury, S.F.,Joseph, L.,Kumar, S.,Tulsidas, S.R.,Bhat, S.,Ziomek, E.,Nard, R.M.,Sivaraman, J.,Purisima, E.O. (登録日: 2007-11-12, 公開日: 2008-03-18, 最終更新日: 2024-11-13)

主引用文献

Chowdhury, S.F.,Joseph, L.,Kumar, S.,Tulsidas, S.R.,Bhat, S.,Ziomek, E.,Menard, R.,Sivaraman, J.,Purisima, E.O.
Exploring inhibitor binding at the S' subsites of cathepsin L
J.Med.Chem., 51:1361-1368, 2008

PubMed Abstract: We report a series of noncovalent, reversible inhibitors of cathepsin L that have been designed to explore additional binding interactions with the S' subsites. The design was based on our previously reported crystal structure that suggested the possibility of engineering increased interactions with the S' subsites ( Chowdhury et al. J. Med. Chem. 2002, 45, 5321-5329 ). A representative of these new inhibitors has been co-crystallized with mature cathepsin L, and the structure has been solved and refined at 2.2 A. The inhibitors described in this work extend farther into the S' subsites of cathepsins than any inhibitors reported in the literature thus far. These interactions appear to make use of a S3' subsite that can potentially be exploited for enhanced specificity and/or affinity.

PubMed: 18278855
DOI: 10.1021/jm701190v

実験手法

X-RAY DIFFRACTION (2.2 Å)