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An allosteric site enables fine‐tuning of cathepsin K by diverse effectors
Author(s) -
Novinec Marko,
Rebernik Mateja,
Lenarčič Brigita
Publication year - 2016
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 - 10.1002/1873-3468.12495
Subject(s) - allosteric regulation , allosteric enzyme , effector , chemistry , cathepsin , cysteine , active site , biochemistry , mutagenesis , enzyme , binding site , cathepsin s , cathepsin k , cathepsin l , mutation , receptor , osteoclast , gene
The cysteine peptidase cathepsin K is a potent collagenolytic enzyme and a promising target for the treatment of osteoporosis. Here, we characterize its allosteric fine‐tuning via a recently identified allosteric site. We show that compound NSC94914 binds this site and acts as a specific partial inhibitor of the collagenolytic activity of cathepsin K. We link the functional differences between NSC94914 and known effectors (compound NSC11345 and glycosaminoglycans) to their different modes of interaction with the site. We characterize the allosteric site by site‐directed mutagenesis and show that it is involved in specific regulation of the collagenolytic activity of cathepsin K.