1CSB

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

Summary for 1CSB

• Entry DOI: 10.2210/pdb1csb/pdb
• Related PRD ID: PRD_000310
• Descriptor: CATHEPSIN B light chain, CATHEPSIN B heavy chain, N-[(3R)-4-ethoxy-3-hydroxy-4-oxobutanoyl]-L-isoleucyl-L-proline, ... (4 entities in total)
• Functional Keywords: papain-like lysosomal dicarboxy-peptidase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Lysosome: P07858 P07858
• Total number of polymer chains: 4
• Total formula weight: 56048.33

Authors

Turk, D.,Bode, W. (deposition date: 1994-12-09, release date: 1996-04-03, Last modification date: 2024-11-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2 Å)