S-S bridges of cathepsin B and H from bovine spleen: a basis for cathepsin B model building and possible functional implications for discrimination between exo- and endopeptidase activities among cathepsins B, H and L
Language English Country Germany Media print
Document type Journal Article
PubMed
1801725
Knihovny.cz E-resources
- MeSH
- Cysteine chemistry MeSH
- Cysteine Endopeptidases * MeSH
- Disulfides chemistry MeSH
- Endopeptidases chemistry MeSH
- Exopeptidases MeSH
- Cathepsin B chemistry MeSH
- Cathepsin H MeSH
- Cathepsin L MeSH
- Cathepsins chemistry MeSH
- Protein Conformation MeSH
- Models, Molecular MeSH
- Molecular Sequence Data MeSH
- Peptide Hydrolases chemistry MeSH
- Amino Acid Sequence MeSH
- Sequence Homology, Nucleic Acid MeSH
- Cattle MeSH
- Spleen enzymology MeSH
- Binding Sites MeSH
- Animals MeSH
- Check Tag
- Cattle MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Cysteine MeSH
- Cysteine Endopeptidases * MeSH
- Disulfides MeSH
- Endopeptidases MeSH
- Exopeptidases MeSH
- Cathepsin B MeSH
- Cathepsin H MeSH
- Cathepsin L MeSH
- Cathepsins MeSH
- Peptide Hydrolases MeSH
Bovine spleen cathepsin B contains 7 disulfide bridges. Using different chemical and enzymatic cleavage methods we isolated fragments representing the individual disulfides: Cys14-Cys43, Cys26-Cys71, Cys62-Cys128, Cys63-Cys67, Cys100-Cys132, Cys108-Cys119, and Cys148-Cys252. A similar line of approach was applied to determine the S-S bridges of bovine spleen cathepsin H: Cys23-Cys66, Cys57-Cys99, Cys157-Cys207, and Cys212-Cys5A, where Cys5A is located in the propart portion of the procathepsin H chain. On the basis of the knowledge of the S-S bridges of cathepsin B a novel sequence alignment of papain and cathepsin B has been proposed. This enabled us to construct a reasonable 3D-model of cathepsin B and propose the region (a 18 residue insertion between Glu89 and Gly90 of papain) responsible for the carboxypeptidase activity of cathepsin B functioning as a "closure". A similar approach was applied to explain the aminopeptidase activity of cathepsin H. A general model of steric regulation of accessibility of the preformed "endopeptidase-like" binding cleft by distant parts of the polypeptide chain of the proteinases discussed is proposed as a factor determining the mode of binding and thus cleavage of polypeptide substrates.
