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The crystal structure of human cathepsin L complexed with E‐64
Author(s) -
Fujishima Akira,
Imai Yumi,
Nomura Toshiyuki,
Fujisawa Yukio,
Yamamoto Yoshio,
Sugawara Tohru
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00216-0
Subject(s) - cathepsin o , cathepsin a , cathepsin b , cathepsin , chemistry , cathepsin l1 , proteases , cysteine , biochemistry , cathepsin h , stereochemistry , cathepsin l , moiety , enzyme , cathepsin s , active site , cathepsin c , microbiology and biotechnology , biology
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 S 2 pocket of cathepsin L is shallow and narrow compared to that of cathepsin B. (3) The S 3 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.