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Prediction of the tertiary structure and substrate binding site of caspase‐8
Author(s) -
Chou Kuo-Chen,
Jones David,
Heinrikson Robert L
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)01246-5
Subject(s) - protein tertiary structure , binding site , substrate (aquarium) , chemistry , biophysics , biochemistry , biology , ecology
The caspases represent a family of sulfhydryl proteases that play important regulatory roles in the cell. The tertiary structure of the protease domain of caspase‐8, also called FLICE, has been predicted by a segment match modeling procedure. First, the atomic coordinates of the catalytic domain of caspase‐3, also called CPP32, a member of the family that is closely related to caspase‐8, were determined based upon the crystal structure of human caspase‐1 (interleukin converting enzyme). Then, the caspase‐3 structure was used as a template for modeling the protease domain of caspase‐8. The resulting structure shows the expected level of similarity with the conformations of caspases‐1 and ‐3 for which crystal structures have been determined. Moreover, the subsite contacts between caspase‐8 and the covalently linked inhibitor, Ac‐DEVD‐aldehyde, are only slightly different from those seen in the caspase‐3 enzyme/inhibitor complex. The model of caspase‐8 can serve as a reference for subsite analysis relative to design of enzyme inhibitors that may find therapeutic application.