The crystal structure of human cathepsin L complexed with E‐64

FEBS Letters

Sugawara, Tohru¹  Yamamoto, Yoshio¹  Fujishima, Akira¹  Nomura, Toshiyuki²  Fujisawa, Yukio²  Imai, Yumi¹ 

[1]Molecular Chemistry Laboratory, Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., Juso-honmachi 2-17-85, Yodogawa-ku, Osaka 532, Japan

[2]Molecular Pharmacology Laboratory, Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., Juso-honmachi 2-17-85, Yodogawa-ku, Osaka 532, Japan

关键词: Cathepsin L;    E-64;    X-ray crystal structure;    E-64;    1-[l-N-(trans-epoxysuccinyl)leucyl]amino-4-guanidinobutane;    RMS;    root mean square;    Bis-Tris;    bis(2-hydroxyethyl)iminotris(hydroxymethyl)methane;   

DOI  :  10.1016/S0014-5793(97)00216-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We have determined the three dimensional structure of the complex of human cathepsin L and E-64, an irreversible inhibitor of cysteine proteases, at 2.5 Å resolution. The overall structure was similar to that of other known cysteine proteases and apparently identical to the mature region of procathepsin L. The electron density for E-64 is clearly visible except for the guanidinobutane moiety. From comparison of the active sites of cathepsin L and B, we found the following: (1) The S′ subsites of cathepsin L and B are totally different because of the `occluding loop' lying on the end of the S′ subsites of cathepsin B. (2) The S₂ pocket of cathepsin L is shallow and narrow compared to that of cathepsin B. (3) The S₃ subsites of the two enzymes are more similar than the other subsites, but cathepsin L may accommodate a more bulky group at this site. Knowledge of the active site structure of cathepsin L should be helpful for the structure-based design of potent and specific inhibitors which are of therapeutic importance.

【 授权许可】

Unknown