1CSB

Crystal structure of cathepsin b inhibited with CA030 at 2.1 angstroms resolution: A basis for the design of specific epoxysuccinyl inhibitors

1CSB の概要

• エントリーDOI: 10.2210/pdb1csb/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000310
• 分子名称: CATHEPSIN B light chain, CATHEPSIN B heavy chain, N-[(3R)-4-ethoxy-3-hydroxy-4-oxobutanoyl]-L-isoleucyl-L-proline, ... (4 entities in total)
• 機能のキーワード: papain-like lysosomal dicarboxy-peptidase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Lysosome: P07858 P07858
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 56048.33

構造登録者

Turk, D.,Bode, W. (登録日: 1994-12-09, 公開日: 1996-04-03, 最終更新日: 2024-11-20)

主引用文献

Turk, D.,Podobnik, M.,Popovic, T.,Katunuma, N.,Bode, W.,Huber, R.,Turk, V.
Crystal structure of cathepsin B inhibited with CA030 at 2.0-A resolution: A basis for the design of specific epoxysuccinyl inhibitors.
Biochemistry, 34:4791-4797, 1995

PubMed Abstract: Crystals of cysteine protease human cathepsin B inhibited with CA030 (ethyl ester of epoxysuccinyl-Ile-Pro-OH) [Murata, M., et al. (1991) FEBS Lett. 280, 307-310; Towatari, T., et al. (1991) FEBS Lett. 280, 311-315] were isomorphous to a previous published structure of cathepsin B [Musil, D., et al. (1991) EMBO J. 10, 2321-2330]. The crystal structure of the complex was refined at 2.0-A resolution to an R-value of 0.194. CA030 is well-defined in the electron density. The Ile-Pro-OH part of CA030 mimics a substrate P1' and P2' residues. The structure thus reveals for the first time a substratelike interaction in the S1' and S2' sites of a papain-like cysteine protease. The CA030 ethyl ester group occupies the S2 site. The structure confirms the role of residues His 110 and His 111 as the receptors of a peptidic substrate C-terminal carboxylic group. The structure suggests that an epoxysuccinyl fragment can be used to extend binding into primed and nonprimed substrate binding sites of a papain-like cysteine protease.

PubMed: 7718586
DOI: 10.1021/bi00014a037

実験手法

X-RAY DIFFRACTION (2 Å)