Selectivity of propeptide-enzyme interaction in cathepsin L-like cysteine proteases
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Klaus Schilling
Abstract
Cathepsin L-like endopeptidases of the papain family are synthesized as proenzymes. N-terminal proregions are essential for folding and latency of the enzyme unit. While selectivity has been reported for the inhibitory function of papain-family propeptides, there is no systematic investigation of the selectivity of their chaperone-like function to date. The chaperone-like cross-reactivity between the cathepsins S, K, and L were thoroughly quantified in trans-experiments, i.e., with isolated propeptides and mature enzymes, and compared to the inhibitory cross-reactivity. The three endopeptidases have been chosen due to only minimal evolutionary distance and nearly identical X-ray structures of their zymogenes. The intramolecular chaperone function of the proregion was found to be more selective than the inhibitory activity and significant differences were found between the selectivity profiles, underlining the assumption that the inhibitory and the chaperone-like propeptide functions are autonomous. Considering the data published on the intramolecular chaperone-like propeptide function within other protease classes as well, our data suggest that intrinsically structured propeptides are more selective than intrinsically unstructured propeptides, i.e., those adopting tertiary structure elements only in complex with their maternal enzyme.
©2009 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- Minireview
- Functional genetic mouse models: promising tools for investigation of the proteolytic internet
- Protein Structure and Function
- Primary sequence, together with other factors, influence peptide deimination by peptidylarginine deiminase-4
- Mercury and cadmium trigger expression of the copper importer Ctr1B, which enables Drosophila to thrive on heavy metal-loaded food
- Cell Biology and Signaling
- Interferon-γ-mediated pathways and in vitro PBMC proliferation in HIV-infected patients
- Exploring the pathogenesis of renal cell carcinoma: pathway and bioinformatics analysis of dysregulated genes and proteins
- Aptamers selected against the unglycosylated EGFRvIII ectodomain and delivered intracellularly reduce membrane-bound EGFRvIII and induce apoptosis
- Involvement of heparan sulfate proteoglycans in cellular uptake of high molecular weight kininogen
- Overexpression of Pygopus2 protects HeLa cells from vinblastine-induced apoptosis
- Proteolysis
- Selectivity of propeptide-enzyme interaction in cathepsin L-like cysteine proteases
- Murine and human cathepsin B exhibit similar properties: possible implications for drug discovery
- Novel Techniques
- Isotope tracing enhancement of chemiluminescence assays for nitric oxide research
