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 |
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Format: | Artikel |
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. |
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ISSN: | 0014-5793 1873-3468 |
DOI: | 10.1016/S0014-5793(97)00216-0 |