3C9E

Crystal structure of the cathepsin K : chondroitin sulfate complex.

Summary for 3C9E

• Entry DOI: 10.2210/pdb3c9e/pdb
• Descriptor: Cathepsin K, 2-acetamido-2-deoxy-4-O-sulfo-beta-D-galactopyranose-(1-4)-beta-D-glucopyranuronic acid-(1-3)-2-acetamido-2-deoxy-4-O-sulfo-beta-D-galactopyranose-(1-4)-beta-D-glucopyranuronic acid-(1-3)-2-acetamido-2-deoxy-4-O-sulfo-beta-D-galactopyranose-(1-4)-beta-D-glucopyranuronic acid, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: n:1 cathepsin k : chondroitin sulfate complex, "beads-on-a-string" organization, hydrolase, lysosome, protease, thiol protease
• Biological source: Homo sapiens (Human)
• Cellular location: Lysosome: P43235
• Total number of polymer chains: 1
• Total formula weight: 25320.14

Authors

Kienetz, M.,Cherney, M.M.,James, M.N.G.,Bromme, D. (deposition date: 2008-02-15, release date: 2008-08-26, Last modification date: 2024-11-13)

Primary citation

Li, Z.,Kienetz, M.,Cherney, M.M.,James, M.N.,Bromme, D.
The crystal and molecular structures of a cathepsin K:chondroitin sulfate complex.
J.Mol.Biol., 383:78-91, 2008

PubMed Abstract: Cathepsin K is the major collagenolytic enzyme produced by bone-resorbing osteoclasts. We showed earlier that the unique triple-helical collagen-degrading activity of cathepsin K depends on the formation of complexes with bone-or cartilage-resident glycosaminoglycans, such as chondroitin 4-sulfate (C4-S). Here, we describe the crystal structure of a 1:n complex of cathepsin K:C4-S inhibited by E64 at a resolution of 1.8 A. The overall structure reveals an unusual "beads-on-a-string"-like organization. Multiple cathepsin K molecules bind specifically to a single cosine curve-shaped strand of C4-S with each cathepsin K molecule interacting with three disaccharide residues of C4-S. One of the more important sets of interactions comes from a single turn of helix close to the N terminus of the proteinase containing a basic amino acid triplet (Arg8-Lys9-Lys10) that forms multiple hydrogen bonds either to the caboxylate or to the 4-sulfate groups of C4-S. Altogether, the binding sites with C4-S are located in the R-domain of cathepsin K and are distant from its active site. This explains why the general proteolytic activity of cathepsin K is not affected by the binding of chondroitin sulfate. Biochemical analyses of cathepsin K and C4-S mixtures support the presence of a 1:n complex in solution; a dissociation constant, K(d), of about 10 nM was determined for the interaction between cathepsin K and C4-S.

PubMed: 18692071
DOI: 10.1016/j.jmb.2008.07.038

Experimental method

X-RAY DIFFRACTION (1.8 Å)