Toward Computer-Based Cleavage Site Prediction of Cysteine Endopeptidases
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T. Lohmüller
Abstract
Identification of relevant substrates is essential for elucidation of in vivo functions of peptidases. The recent availability of the complete genome sequences of many eukaryotic organisms holds the promise of identifying specific peptidase substrates by systematic proteome analyses in combination with computer based screening of genome databases. Currently available proteomics and bioinformatics tools are not sufficient for reliable endopeptidase substrate predictions. To address these shortcomings the bioinformatics tool 'PEPS' (Prediction of Endopeptidase Substrates) has been developed and is presented here. PEPS uses individual rule-based endopeptidase cleavage site scoring matrices (CSSM). The efficiency of PEPS in predicting putative caspase 3, cathepsin B and cathepsin L cleavage sites is demonstrated in comparison to established algorithms. Mortalin, a member of the heat shock protein family HSP70, was identified by PEPS as a putative cathepsin L substrate. Comparative proteome analyses of cathepsin L-deficient and wildtype mouse fibroblasts showed that mortalin is enriched in the absence of cathepsin L. These results indicate that CSSM/PEPS can correctly predict relevant peptidase substrates.
Copyright © 2003 by Walter de Gruyter GmbH & Co. KG
Articles in the same Issue
- Vito Turk – 30 Years of Research on Cysteine Proteases and Their Inhibitors
- Family C1 Cysteine Proteases: Biological Diversity or Redundancy?
- Molecular Regulation of Human Cathepsin B: Implication in Pathologies
- Caspases and Neuronal Development
- Structural Basis of the Matrix Metalloproteinases and Their Physiological Inhibitors, the Tissue Inhibitors of Metalloproteinases
- Managing Peptidases in the Genomic Era
- Insights into the Roles of Cathepsins in Antigen Processing and Presentation Revealed by Specific Inhibitors
- Cleavage Site Specificity of Cathepsin K toward Cartilage Proteoglycans and Protease Complex Formation
- Toward Computer-Based Cleavage Site Prediction of Cysteine Endopeptidases
- Isolation and Characterization of a Novel and Potent Inhibitor of Arg-Gingipain from Streptomyces sp. Strain FA-70
- Procongopain from Trypanosoma congolense Is Processed at Basic pH: An Unusual Feature among Cathepsin L-Like Cysteine Proteases
- Attenuated Kinin Release from Human Neutrophil Elastase-Pretreated Kininogens by Tissue and Plasma Kallikreins
- Effect of Plant Kunitz Inhibitors from Bauhinia bauhinioides and Bauhinia rufa on Pulmonary Edema Caused by Activated Neutrophils
- Revisiting Ubiquity and Tissue Specificity of Human Calpains
- The Calpastatin-Derived Calpain Inhibitor CP1B Reduces mRNA Expression of Matrix Metalloproteinase-2 and -9 and Invasion by Leukemic THP-1 Cells
- Heat Stress-Dependent DNA Binding of Arabidopsis Heat Shock Transcription Factor HSF1 to Heat Shock Gene Promoters in Arabidopsis Suspension Culture Cells in vivo
- T47-D Cells and Type V Collagen: A Model for the Study of Apoptotic Gene Expression by Breast Cancer Cells
Articles in the same Issue
- Vito Turk – 30 Years of Research on Cysteine Proteases and Their Inhibitors
- Family C1 Cysteine Proteases: Biological Diversity or Redundancy?
- Molecular Regulation of Human Cathepsin B: Implication in Pathologies
- Caspases and Neuronal Development
- Structural Basis of the Matrix Metalloproteinases and Their Physiological Inhibitors, the Tissue Inhibitors of Metalloproteinases
- Managing Peptidases in the Genomic Era
- Insights into the Roles of Cathepsins in Antigen Processing and Presentation Revealed by Specific Inhibitors
- Cleavage Site Specificity of Cathepsin K toward Cartilage Proteoglycans and Protease Complex Formation
- Toward Computer-Based Cleavage Site Prediction of Cysteine Endopeptidases
- Isolation and Characterization of a Novel and Potent Inhibitor of Arg-Gingipain from Streptomyces sp. Strain FA-70
- Procongopain from Trypanosoma congolense Is Processed at Basic pH: An Unusual Feature among Cathepsin L-Like Cysteine Proteases
- Attenuated Kinin Release from Human Neutrophil Elastase-Pretreated Kininogens by Tissue and Plasma Kallikreins
- Effect of Plant Kunitz Inhibitors from Bauhinia bauhinioides and Bauhinia rufa on Pulmonary Edema Caused by Activated Neutrophils
- Revisiting Ubiquity and Tissue Specificity of Human Calpains
- The Calpastatin-Derived Calpain Inhibitor CP1B Reduces mRNA Expression of Matrix Metalloproteinase-2 and -9 and Invasion by Leukemic THP-1 Cells
- Heat Stress-Dependent DNA Binding of Arabidopsis Heat Shock Transcription Factor HSF1 to Heat Shock Gene Promoters in Arabidopsis Suspension Culture Cells in vivo
- T47-D Cells and Type V Collagen: A Model for the Study of Apoptotic Gene Expression by Breast Cancer Cells
