Subsite cooperativity in protease specificity
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Natasha M. Ng
Abstract
Proteases play vital roles in a range of biological processes, such as cell cycle, cell growth and differentiation, apoptosis, haemostasis and signalling. Fundamental to our knowledge of protease action is an understanding of how the active site operates; this has been examined through extensive studies of the substrate specificity of the enzymes. Kinetic and structural analyses have shown that the binding of a particular substrate residue at a protease subsite can have either a positive or negative influence on the binding of particular residues at other subsites. This phenomenon has been termed subsite cooperativity and has been observed in a wide range of proteases, often between non-adjacent subsites. This review aims to highlight studies where subsite cooperativity has been observed, experimental techniques used in the past and potential methods that can be employed to comprehensively examine this phenomenon. Further understanding of how the protease active site recognises and chooses its substrates for cleavage will have a significant impact on the development of pharmaceuticals that target these enzymes.
©2009 by Walter de Gruyter Berlin New York
Articles in the same Issue
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- Activation mechanisms of coagulation factor IX
- Subsite cooperativity in protease specificity
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- 3D structure of a binary ROP-PRONE complex: the final intermediate for a complete set of molecular snapshots of the RopGEF reaction
- Identification and characterization of a bioactive lantibiotic produced by Staphylococcus warneri
- Role of the polypeptide backbone and post-translational modifications in cross-reactivity of Art v 1, the major mugwort pollen allergen
- Cell Biology and Signaling
- Short double-stranded RNAs of specific sequence activate ribosomal TAK1-D and induce a global inhibition of translation
- Krüppel-like factor 4 represses transcription of the survivin gene in esophageal cancer cell lines
- Proteolysis
- Release of endo-lysosomal cathepsins B, D, and L from IEC6 cells in a cell culture model mimicking intestinal manipulation
- Cathepsin B release from rodent intestine mucosa due to mechanical injury results in extracellular matrix damage in early post-traumatic phases
- Identification of parasite-responsive cysteine proteases in Manduca sexta
- Cooperative effects in the substrate specificity of the complement protease C1s
- Novel Techniques
- The influenza A virus matrix protein as a marker to monitor initial virus internalisation
- Erratum
- Murine and human cathepsin B exhibit similar properties: possible implications for drug discovery
Articles in the same Issue
- Reviews
- The liaison between apoptotic cells and macrophages – the end programs the beginning
- Activation mechanisms of coagulation factor IX
- Subsite cooperativity in protease specificity
- Minireview
- Retrodifferentiation – a mechanism for cellular regeneration?
- Protein Structure and Function
- The solution structure of pGolemi, a high affinity Mena EVH1 binding miniature protein, suggests explanations for paralog-specific binding to Ena/VASP homology (EVH) 1 domains
- 3D structure of a binary ROP-PRONE complex: the final intermediate for a complete set of molecular snapshots of the RopGEF reaction
- Identification and characterization of a bioactive lantibiotic produced by Staphylococcus warneri
- Role of the polypeptide backbone and post-translational modifications in cross-reactivity of Art v 1, the major mugwort pollen allergen
- Cell Biology and Signaling
- Short double-stranded RNAs of specific sequence activate ribosomal TAK1-D and induce a global inhibition of translation
- Krüppel-like factor 4 represses transcription of the survivin gene in esophageal cancer cell lines
- Proteolysis
- Release of endo-lysosomal cathepsins B, D, and L from IEC6 cells in a cell culture model mimicking intestinal manipulation
- Cathepsin B release from rodent intestine mucosa due to mechanical injury results in extracellular matrix damage in early post-traumatic phases
- Identification of parasite-responsive cysteine proteases in Manduca sexta
- Cooperative effects in the substrate specificity of the complement protease C1s
- Novel Techniques
- The influenza A virus matrix protein as a marker to monitor initial virus internalisation
- Erratum
- Murine and human cathepsin B exhibit similar properties: possible implications for drug discovery
