ArticleMolecular & cellular proteomics : MCP2013
Nepenthesin from monkey cups for hydrogen/deuterium exchange mass spectrometry.
Article in Molecular & cellular proteomics : MCP, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 66 citations in OpenAlex.
- Mass Spectrometry-Based De Novo Sequencing of N-Glycosylated Light Chains: Linking Urinary Proteoforms to In Situ Renal Amyloid Deposits.Molecular & cellular proteomics : MCP · 2026Article
- A Native Nepenthesin Reactor for Improved Proteolytic Digestion of Intrinsically Disordered Proteins in Proteomics Workflows.Chembiochem : a European journal of chemical biology · 2026Article
- DigDig: A Software for In-Depth Analysis and Comparison of Proteolytic Digestion.Analytical chemistry · 2025Article
- Identification of a direct interaction between the Fab domains of IgG antibodies and human FcRn upon IgG-FcRn complex formation.Communications biology · 2025Article
- Fundamentals of HDX-MS.Essays in biochemistry · 2023Review
- Hydrogen Deuterium Exchange and other Mass Spectrometry-based Approaches for Epitope Mapping.Frontiers in analytical science · 2023Article
- Advances in Hydrogen/Deuterium Exchange Mass Spectrometry and the Pursuit of Challenging Biological Systems.Chemical reviews · 2022Review
- Barley Nepenthesin-Like Aspartic ProteaseFrontiers in plant science · 2021Article
- Extensive flavivirus E trimer breathing accompanies stem zippering of the post-fusion hairpin.EMBO reports · 2020Article
- A glimpse into the molecular mechanism of integral membrane proteins through hydrogen-deuterium exchange mass spectrometry.Protein science : a publication of the Protein Society · 2020Review
- Molecular Properties and New Potentials of Plant Nepenthesins.Plants (Basel, Switzerland) · 2020Review
- Chasing Tails: Cathepsin-L Improves Structural Analysis of Histones by HX-MS.Molecular & cellular proteomics : MCP · 2019Article
- High-Resolution HDX-MS of Cytochrome c Using Pepsin/Fungal Protease Type XIII Mixed Bed Column.Journal of the American Society for Mass Spectrometry · 2019Article
- Tracking Higher Order Protein Structure by Hydrogen-Deuterium Exchange Mass Spectrometry.Protein and peptide letters · 2019Review
- Determination of Backbone Amide Hydrogen Exchange Rates of Cytochrome c Using Partially Scrambled Electron Transfer Dissociation Data.Journal of the American Society for Mass Spectrometry · 2018Article
- Aspergillus niger Prolyl Endoprotease for Hydrogen-Deuterium Exchange Mass Spectrometry and Protein Structural Studies.Analytical chemistry · 2017Article
- Structural and functional characterization of the PNKP-XRCC4-LigIV DNA repair complex.Nucleic acids research · 2017Article
- Neprosin, a Selective Prolyl Endoprotease for Bottom-up Proteomics and Histone Mapping.Molecular & cellular proteomics : MCP · 2017Article
- Regio-Selective Intramolecular Hydrogen/Deuterium Exchange in Gas-Phase Electron Transfer Dissociation.Journal of the American Society for Mass Spectrometry · 2017Article
- Determination of Equine Cytochrome c Backbone Amide Hydrogen/Deuterium Exchange Rates by Mass Spectrometry Using a Wider Time Window and Isotope Envelope.Journal of the American Society for Mass Spectrometry · 2017Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Studies of protein dynamics, structure and interactions using hydrogen/deuterium exchange mass spectrometry (HDX-MS) have sharply increased over the past 5-10 years. The predominant technology requires fast digestion at pH 2-3 to retain deuterium label. Pepsin is used almost exclusively, but it provides relatively low efficiency under the constraints of the experiment, and a selectivity profile that renders poor coverage of intrinsically disordered regions. In this study we present nepenthesin-containing secretions of the pitcher plant Nepenthes, commonly called monkey cups, for use in HDX-MS. We show that nepenthesin is at least 1400-fold more efficient than pepsin under HDX-competent conditions, with a selectivity profile that mimics pepsin in part, but also includes efficient cleavage C-terminal to "forbidden" residues K, R, H, and P. High efficiency permits a solution-based analysis with no detectable autolysis, avoiding the complication of immobilized enzyme reactors. Relaxed selectivity promotes high coverage of disordered regions and the ability to "tune" the mass map for regions of interest. Nepenthesin-enriched secretions were applied to an analysis of protein complexes in the nonhomologous end-joining DNA repair pathway. The analysis of XRCC4 binding to the BRCT domains of Ligase IV points to secondary interactions between the disordered C-terminal tail of XRCC4 and remote regions of the BRCT domains, which could only be identified with a nepenthesin-based workflow. HDX data suggest that stalk-binding to XRCC4 primes a BRCT conformation in these remote regions to support tail interaction, an event which may be phosphoregulated. We conclude that nepenthesin is an effective alternative to pepsin for all HDX-MS applications, and especially for the analysis of structural transitions among intrinsically disordered proteins and their binding partners.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.