Cathepsin research is one of the most progressive areas in proteolysis. Cathepsins are a diverse group of eukaryotic peptidases belonging to the aspartic, cysteine and serine classes. They act as both non-specific proteases and as specific processing enzymes in numerous physiological and pathological processes. In humans, their dysregulation is associated with severe pathologies, such as cancer, cardiovascular and neurodegenerative diseases, arthritis, and osteoporosis. Proteolytic systems controlled by cathepsins are a critical part of host-pathogen and host-parasite interactions as demonstrated for cathepsin-like peptidases from, e.g., hematophagous parasites, herbivorous insects and plants. Because of the broad involvement of cathepsins in pathological processes, they are among today’s top-priority drug targets. This review provides an update on the structure and function of pathology-associated cathepsins in humans and human parasites.
- MeSH
- aspartátové proteasy fyziologie chemie MeSH
- chemie farmaceutická MeSH
- cysteinové proteasy fyziologie chemie MeSH
- endopeptidasy fyziologie chemie MeSH
- inhibitory proteas * chemie MeSH
- kathepsiny * biosyntéza fyziologie chemie klasifikace MeSH
- lidé MeSH
- parazitární nemoci * krev MeSH
- patologické procesy * etiologie MeSH
- proteolýza * MeSH
- racionální návrh léčiv MeSH
- serinové proteasy fyziologie chemie MeSH
- výzkum MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Intramembrane proteases cleave membrane proteins in their transmembrane helices to regulate a wide range of biological processes. They catalyse hydrolytic reactions within the hydrophobic environment of lipid membranes where water is normally excluded. How? Do the different classes of intramembrane proteases share any mechanistic principles? In this review these questions will be discussed in view of the crystal structures of prokaryotic members of the three known catalytic types of intramembrane proteases published over the past 7 years. Rhomboids, the intramembrane serine proteases that are the best understood family, will be the initial area of focus, and the principles that have arisen from a number of structural and biochemical studies will be considered. The site-2 metalloprotease and GXGD-type aspartyl protease structures will then be discussed, with parallels drawn and differences highlighted between these enzymes and the rhomboids. Despite the significant advances achieved so far, to obtain a detailed understanding of the mechanism of any intramembrane protease, high-resolution structural information on the substrate-enzyme complex is required. This remains a major challenge for the field.
- MeSH
- aminokyselinové motivy MeSH
- aspartátové proteasy chemie metabolismus MeSH
- bakteriální proteiny chemie metabolismus MeSH
- DNA vazebné proteiny chemie MeSH
- endopeptidasy chemie metabolismus MeSH
- katalytická doména MeSH
- konformace proteinů MeSH
- membránové proteiny chemie metabolismus MeSH
- metaloendopeptidasy chemie metabolismus MeSH
- molekulární evoluce MeSH
- molekulární sekvence - údaje MeSH
- preseniliny chemie metabolismus MeSH
- proteiny Drosophily chemie metabolismus MeSH
- proteiny z Escherichia coli chemie MeSH
- proteolýza MeSH
- sekvence aminokyselin MeSH
- serinové proteasy chemie metabolismus MeSH
- substrátová specifita MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
