5JA7

Human cathepsin K mutant C25S in complex with the allosteric effector NSC94914

Summary for 5JA7

• Entry DOI: 10.2210/pdb5ja7/pdb
• Descriptor: Cathepsin K, [([1,1'-biphenyl]-2-yl)methyl]propanedioic acid, SULFATE ION, ... (6 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: 2
• Total formula weight: 49962.92

Authors

Novinec, M.,Korenc, M.,Lenarcic, B. (deposition date: 2016-04-12, release date: 2016-11-30, Last modification date: 2024-10-16)

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

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

Experimental method

X-RAY DIFFRACTION (1.61 Å)