ArticleChemical science2015
Fluorine teams up with water to restore inhibitor activity to mutant BPTI.
Article in Chemical science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 38 citations in OpenAlex.
- Toward Grid-Based Models for Molecular Association.Journal of chemical theory and computation · 2025Article
- Computational screening of the effects of mutations on protein-protein off-rates and dissociation mechanisms by τRAMD.Communications biology · 2024Article
- Prebound State Discovered in the Unbinding Pathway of Fluorinated Variants of the Trypsin-BPTI Complex Using Random Acceleration Molecular Dynamics Simulations.Journal of chemical information and modeling · 2024Article
- Fluorinated Protein-Ligand Complexes: A Computational Perspective.The journal of physical chemistry. B · 2024Review
- Non-Canonical Amino Acids in Analyses of Protease Structure and Function.International journal of molecular sciences · 2023Review
- The Nϵ-Rule for Serine, but Not Cysteine Catalytic Triads.Angewandte Chemie (International ed. in English) · 2022Article
- Molecular Characterization of Kunitz-Type Protease Inhibitors from Blister Beetles (Coleoptera, Meloidae).Biomolecules · 2022Article
- Fluorine-induced polarity increases inhibitory activity of BPTI towards chymotrypsin.RSC chemical biology · 2022Article
- Identification of 13 Guanidinobenzoyl- or Aminidinobenzoyl-Containing Drugs to Potentially Inhibit TMPRSS2 for COVID-19 Treatment.International journal of molecular sciences · 2021Article
- Molecular mechanism of inhibiting the SARS-CoV-2 cell entry facilitator TMPRSS2 with camostat and nafamostat.Chemical science · 2021Article
- Targeted Fluoro Positioning for the Discovery of a Potent and Highly Selective Matrix Metalloproteinase Inhibitor.ChemistryOpen · 2017Article
- Discovery and Investigation of Natural Editing Function against Artificial Amino Acids in Protein Translation.ACS central science · 2017Article
- Position-dependent impact of hexafluoroleucine and trifluoroisoleucine on protease digestion.Beilstein journal of organic chemistry · 2017Article
- An Acrobatic Substrate Metamorphosis Reveals a Requirement for Substrate Conformational Dynamics in Trypsin Proteolysis.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Introducing fluorine into molecules has a wide range of effects on their physicochemical properties, often desirable but in most cases unpredictable. The fluorine atom imparts the C-F bond with low polarizability and high polarity, and significantly affects the behavior of neighboring functional groups, in a covalent or noncovalent manner. Here, we report that fluorine, present in the form of a single fluoroalkyl amino acid side chain in the P1 position of the well-characterized serine-protease inhibitor BPTI, can fully restore inhibitor activity to a mutant that contains the corresponding hydrocarbon side chain at the same site. High resolution crystal structures were obtained for four BPTI variants in complex with bovine β-trypsin, revealing changes in the stoichiometry and dynamics of water molecules in the S1 subsite. These results demonstrate that the introduction of fluorine into a protein environment can result in "chemical complementation" that has a significantly favorable impact on protein-protein interactions.
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Registered trials
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.