Turk D, Podobnik M, Popovic T, Katunuma N, Bode W, Huber R, Turk V
Department of Biochemistry and Molecular Biology, Jozef Stefan Institute, Ljubljana, Slovenia.
Biochemistry. 1995 Apr 11;34(14):4791-7. doi: 10.1021/bi00014a037.
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.
用CA030（环氧琥珀酰 - 异亮氨酸 - 脯氨酸 - 羟基乙酯）抑制的人组织蛋白酶B半胱氨酸蛋白酶晶体[村田，M.等人（1991年）《欧洲生物化学学会联合会快报》280，307 - 310；户刈，T.等人（1991年）《欧洲生物化学学会联合会快报》280，311 - 315]与先前发表的组织蛋白酶B结构[穆西尔，D.等人（1991年）《欧洲分子生物学组织杂志》10，2321 - 2330]同晶型。该复合物的晶体结构在2.0埃分辨率下精修至R值为0.194。CA030在电子密度图中定义明确。CA030的异亮氨酸 - 脯氨酸 - 羟基部分模拟底物的P1'和P2'残基。因此，该结构首次揭示了类木瓜蛋白酶半胱氨酸蛋白酶S1'和S2'位点中的底物样相互作用。CA030乙酯基团占据S2位点。该结构证实了His 110和His 111残基作为肽底物C末端羧基受体的作用。该结构表明环氧琥珀酰片段可用于扩展与类木瓜蛋白酶半胱氨酸蛋白酶的引发和未引发底物结合位点的结合。
