Avtor/Urednik		Turk, D; Podobnik, M; Popovič, T; Katunuma, N; Bode, W; Huber, R; Turk, V
Naslov		Crystal structure of cathepsin B inhibited with CA030 at 2.0-A resolution: A basis for the design of specific epoxysuccinyl inhibitors
Tip		članek
Vir		Biochemistry
Vol. in št.		Letnik 34, št. 14
Leto izdaje		1995
Obseg		str. 4791-7
Jezik		eng
Abstrakt		Crystals of cysteine protease human cathepsin B inhibited with CA030 (ethyl ester of epoxysuccinyl-Ile-Pro-OH) ŠMurata, M., et al. (1991) FEBS Lett. 280, 307-310; Towatari, T., et al. (1991) FEBS Lett. 280, 311-315Ć were isomorphous to a previous published structure of cathepsin B ŠMusil, D., et al. (1991) EMBO J. 10, 2321-2330Ć. 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.
Deskriptorji		CATHEPSIN B DIPEPTIDES AMINO ACID SEQUENCE BINDING SITES CATHEPSIN B CRYSTALLOGRAPHY, X-RAY DIPEPTIDES DRUG DESIGN LEUCINE MOLECULAR SEQUENCE DATA PROTEIN CONFORMATION