The crystal structure of human cathepsin L complexed with E-64
Abstract
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.
- Publication:
-
FEBS Letters
- Pub Date:
- January 1997
- DOI:
- 10.1016/S0014-5793(97)00216-0
- Bibcode:
- 1997FEBSL.407...47F
- Keywords:
-
- 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