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

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 procathe...

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Veröffentlicht in:FEBS letters 1997-04, Vol.407 (1), p.47-50
Hauptverfasser: Fujishima, Akira, Imai, Yumi, Nomura, Toshiyuki, Fujisawa, Yukio, Yamamoto, Yoshio, Sugawara, Tohru
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Sprache:eng
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Zusammenfassung: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.
ISSN:0014-5793
1873-3468
DOI:10.1016/S0014-5793(97)00216-0