1by8
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| , resolution 2.6Å | |||||||
|---|---|---|---|---|---|---|---|
| Activity: | Cathepsin K, with EC number 3.4.22.38 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
THE CRYSTAL STRUCTURE OF HUMAN PROCATHEPSIN K
OverviewOverview
Cathepsin K is a cysteine protease present in human osteoclasts that plays an important role in bone resorption. Cathepsin K is synthesized as an inactive proenzyme and activated under conditions of low pH. Autoproteolytic processing of the N-terminal 99 amino acid propeptide produces the active, mature form of cathepsin K. It is presumed that the activation of procathepsin K in vivo occurs in the bone resorption pit, which has a low-pH environment. We have determined the structure of human procathepsin K at 2.8 A resolution. The structure of the mature enzyme domain within procathepsin K is virtually identical to that of mature cathepsin K. The fold of the propeptide of procathepsin K is similar to that observed in procathepsins B and L despite differences in length and sequence. A portion of the propeptide occupies the active site cleft of cathepsin K. Hydrophobic interactions, salt bridges, and hydrogen-bonding interactions are observed in the structure of the propeptide and between the propeptide and the mature enzyme of procathepsin K. These interactions suggest an explanation for the stability of the proenzyme. The structure of procathepsin K contributes to an understanding of the molecular basis of inhibition by the propeptide portion of the molecule and activation of this important member of the cysteine protease family.
DiseaseDisease
Known disease associated with this structure: Pycnodysostosis OMIM:[601105]
About this StructureAbout this Structure
1BY8 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
The crystal structure of human procathepsin K., LaLonde JM, Zhao B, Janson CA, D'Alessio KJ, McQueney MS, Orsini MJ, Debouck CM, Smith WW, Biochemistry. 1999 Jan 19;38(3):862-9. PMID:9893980
Page seeded by OCA on Thu Mar 20 10:17:26 2008