The slow-binding inhibition of cathepsin K by its propeptide.
A peptide corresponding to the full-length proregion (amino acids 16-114) of human cathepsin K was expressed and purified from Escherichia coli. This recombinant propeptide was investigated for its ability to inhibit the activity of three cysteine proteinases: cathepsins K, L, and B. Kinetic studies showed the propeptide to be a potent slow-binding inhibitor of its parent enzyme with a K(i) = 2. 61 nM at pH 6. This inhibition was pH-dependent, with a decrease in pH from 6 to 4 leading to a concomitant increase in K(i) to 147 nM. The propeptide also inhibited cathepsin L with a K(i) = 26.1 nM at pH 6, but showed little inhibition of cathepsin B at concentrations up to 400 nM.
Billington
C J
CJ
Joint Diseases Laboratory, Shriners Hospital for Children, 1529 Cedar Avenue, Montreal, Quebec, H3G 1A6, Canada.
Mason
P
P
Magny
M C
MC
Mort
J S
JS
D000911:Antibodies, Monoclonal / Q000276:immunology; D002401:Cathepsin B / Q000037:antagonists & inhibitors / Q000378:metabolism; D056657:Cathepsin K; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D002942:Circular Dichroism; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D010450:Endopeptidases; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008970:Molecular Weight; D010446:Peptide Fragments / Q000737:chemistry* / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D013379:Substrate Specificity
D000911:Antibodies, Monoclonal; D015853:Cysteine Proteinase Inhibitors; D010446:Peptide Fragments; D011994:Recombinant Proteins; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C118659:procathepsin K; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; C534130:CTSK protein, human; D056657:Cathepsin K