ArticlePloS one2015
Characterizing Protease Specificity: How Many Substrates Do We Need?
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Caspase-3 regulates RNA splicing and mitochondrial dynamics in microglia during Parkinson's disease.Cell death & disease · 2026Article
- Drug Discovery Strategies for Kallikrein-Related Peptidases.International journal of molecular sciences · 2025Review
- Substrate Specificity and Peptide Motif Preferences of β-Lytic and L5 Proteases fromInternational journal of molecular sciences · 2025Article
- Synthetic protein protease sensor platform.Frontiers in bioengineering and biotechnology · 2024Article
- New Insights of Early Brain Injury after Subarachnoid Hemorrhage: A Focus on the Caspase Family.Current neuropharmacology · 2023Article
- Post-Proline Cleaving Enzymes (PPCEs): Classification, Structure, Molecular Properties, and Applications.Plants (Basel, Switzerland) · 2022Review
- Reductive site-selective atypicalScience advances · 2022Article
- Integrating knowledge of protein sequence with protein function for the prediction and validation of new MALT1 substrates.Computational and structural biotechnology journal · 2022Article
- Identification of novel ADAMTS1, ADAMTS4 and ADAMTS5 cleavage sites in versican using a label-free quantitative proteomics approach.Journal of proteomics · 2021Article
- Insights into the phylogeny and transcriptional response of serine proteases in a halotolerant cyanobacteriumPlant signaling & behavior · 2021Article
- Mapping specificity, cleavage entropy, allosteric changes and substrates of blood proteases in a high-throughput screen.Nature communications · 2021Article
- Quantitative profiling of protease specificity.PLoS computational biology · 2021Article
- Cell Death Related Proteins Beyond Apoptosis in the CNS.Frontiers in cell and developmental biology · 2021Review
- Assessing the range of enzymatic and oxidative tunability for biosensor design.Journal of materials chemistry. B · 2020Review
- Twenty years of bioinformatics research for protease-specific substrate and cleavage site prediction: a comprehensive revisit and benchmarking of existing methods.Briefings in bioinformatics · 2019Review
- The conserved metalloprotease invadolysin is present in invertebrate haemolymph and vertebrate blood.Biology open · 2019Article
- An unexpected switch in peptide binding mode: from simulation to substrate specificity.Journal of biomolecular structure & dynamics · 2018Article
- Electrostatic recognition in substrate binding to serine proteases.Journal of molecular recognition : JMR · 2018Article
- Structural determinants of specificity and regulation of activity in the allosteric loop network of human KLK8/neuropsin.Scientific reports · 2018Article
- Block-based characterization of protease specificity from substrate sequence profile.BMC bioinformatics · 2017Article
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Authors and funding
6 authors.
Funding
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Abstract
Calculation of cleavage entropies allows to quantify, map and compare protease substrate specificity by an information entropy based approach. The metric intrinsically depends on the number of experimentally determined substrates (data points). Thus a statistical analysis of its numerical stability is crucial to estimate the systematic error made by estimating specificity based on a limited number of substrates. In this contribution, we show the mathematical basis for estimating the uncertainty in cleavage entropies. Sets of cleavage entropies are calculated using experimental cleavage data and modeled extreme cases. By analyzing the underlying mathematics and applying statistical tools, a linear dependence of the metric in respect to 1/n was found. This allows us to extrapolate the values to an infinite number of samples and to estimate the errors. Analyzing the errors, a minimum number of 30 substrates was found to be necessary to characterize substrate specificity, in terms of amino acid variability, for a protease (S4-S4') with an uncertainty of 5 percent. Therefore, we encourage experimental researchers in the protease field to record specificity profiles of novel proteases aiming to identify at least 30 peptide substrates of maximum sequence diversity. We expect a full characterization of protease specificity helpful to rationalize biological functions of proteases and to assist rational drug design.
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