7pck
From Proteopedia
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CRYSTAL STRUCTURE OF WILD TYPE HUMAN PROCATHEPSIN K
Contents |
Overview
Cathepsin K is a lysosomal cysteine protease belonging to the papain, superfamily. It has been implicated as a major mediator of osteoclastic, bone resorption. Wild-type human procathepsin K has been crystallized in a, glycosylated and a deglycosylated form. The latter crystals diffract, better, to 3.2 A resolution, and contain four molecules in the asymmetric, unit. The structure was solved by molecular replacement and refined to an, R-factor of 0.194. The N-terminal fragment of the proregion forms a, globular domain while the C-terminal segment is extended and shows, substantial flexibility. The proregion interacts with the enzyme along the, substrate binding groove and along the proregion binding loop (residues, Ser138-Asn156). It binds to the active site in the opposite direction to, that of natural substrates. The overall binding mode of the proregion to, cathepsin K is similar to that observed in cathepsin L, caricain, and, cathepsin B, but there are local differences that likely contribute to the, specificity of these proregions for their cognate enzymes. The main, observed difference is in the position of the short helix alpha3p, (67p-75p), which occupies the S' subsites. As in the other proenzymes, the, proregion utilizes the S2 subsite for anchoring by placing a leucine side, chain there, according to the specificity of cathepsin K toward its, substrate.
Disease
Known disease associated with this structure: Pycnodysostosis OMIM:[601105]
About this Structure
7PCK is a Single protein structure of sequence from Homo sapiens. Active as Cathepsin K, with EC number 3.4.22.38 Full crystallographic information is available from OCA.
Reference
Crystal structure of wild-type human procathepsin K., Sivaraman J, Lalumiere M, Menard R, Cygler M, Protein Sci. 1999 Feb;8(2):283-90. PMID:10048321
Page seeded by OCA on Mon Nov 12 23:54:18 2007
