5JH3

Human cathepsin K mutant C25S

Summary for 5JH3

Entry DOI	10.2210/pdb5jh3/pdb
Descriptor	Cathepsin K, SULFATE ION, ACETATE ION, ... (5 entities in total)
Functional Keywords	allostery cysteine, peptidase proteolysis, enzyme regulation, collagenase, hydrolase
Biological source	Homo sapiens (Human)
Cellular location	Lysosome: P43235
Total number of polymer chains	1
Total formula weight	24826.17
Authors	Novinec, M.,Korenc, M.,Lenarcic, B. (deposition date: 2016-04-20, release date: 2016-11-30, Last modification date: 2024-11-20)
Primary citation	Novinec, M.,Rebernik, M.,Lenarcic, B. An allosteric site enables fine-tuning of cathepsin K by diverse effectors. FEBS Lett., 590:4507-4518, 2016 Cited by PubMed Abstract: 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. PubMed: 27859061 DOI: 10.1002/1873-3468.12495 PDB entries with the same primary citation
Experimental method	X-RAY DIFFRACTION (1.75 Å)

Structure validation