1BY8

THE CRYSTAL STRUCTURE OF HUMAN PROCATHEPSIN K

Summary for 1BY8

• Entry DOI: 10.2210/pdb1by8/pdb
• Descriptor: PROTEIN (PROCATHEPSIN K) (1 entity in total)
• Functional Keywords: hydrolase(sulfhydryl proteinase), papain, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Lysosome: P43235
• Total number of polymer chains: 1
• Total formula weight: 35357.90

Authors

Lalonde, J.M.,Zhao, B.,Smith, W.W.,Janson, C.A.,Desjarlais, R.L.,Tomaszek, T.A.,Carr, T.J.,Thompson, S.K.,Yamashita, D.S.,Veber, D.F.,Abdel-Mequid, S.S. (deposition date: 1998-10-27, release date: 1999-10-24, Last modification date: 2024-11-13)

Primary citation

LaLonde, J.M.,Zhao, B.,Janson, C.A.,D'Alessio, K.J.,McQueney, M.S.,Orsini, M.J.,Debouck, C.M.,Smith, W.W.
The crystal structure of human procathepsin K.
Biochemistry, 38:862-869, 1999

PubMed Abstract: 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.

PubMed: 9893980
DOI: 10.1021/bi9822271

Experimental method

X-RAY DIFFRACTION (2.6 Å)