ArticlePloS one2012
Engineering of three-finger fold toxins creates ligands with original pharmacological profiles for muscarinic and adrenergic receptors.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 44 citations in OpenAlex.
- Discerning dangerous gain of function: most gain of function (GoF) research does not involve infectious microbes.Frontiers in bioengineering and biotechnology · 2026Review
- Orphan Three-Finger Toxins from Snake Venoms: Unexplored Library of Novel Biological Ligands with Potential New Structures and Functions.International journal of molecular sciences · 2025Review
- Variations in "Functional Site" Residues and Classification of Three-Finger Neurotoxins in Snake Venoms.Toxins · 2025Review
- Scalable production of recombinant three-finger proteins: from inclusion bodies to high quality molecular probes.Microbial cell factories · 2024Article
- Structural and Functional Diversity of Animal Toxins Interacting With GPCRs.Frontiers in molecular biosciences · 2022Review
- Allosteric Modulator Leads Hiding in Plain Site: Developing Peptide and Peptidomimetics as GPCR Allosteric Modulators.Frontiers in chemistry · 2021Review
- Horse immunization with short-chain consensus α-neurotoxin generates antibodies against broad spectrum of elapid venomous species.Nature communications · 2019Article
- Ancestral protein resurrection and engineering opportunities of the mamba aminergic toxins.Scientific reports · 2017Article
- Evaluation of cytotoxic activities of snake venoms toward breast (MCF-7) and skin cancer (A-375) cell lines.Cytotechnology · 2016Article
- Ringhalexin from Hemachatus haemachatus: A novel inhibitor of extrinsic tenase complex.Scientific reports · 2016Article
- Mambalgin-1 Pain-relieving Peptide, Stepwise Solid-phase Synthesis, Crystal Structure, and Functional Domain for Acid-sensing Ion Channel 1a Inhibition.The Journal of biological chemistry · 2016Article
- Armadillidin H, a Glycine-Rich Peptide from the Terrestrial CrustaceanFrontiers in microbiology · 2016Article
- Crystallization of recombinant green mamba ρ-Da1a toxin during a lyophilization procedure and its structure determination.Acta crystallographica. Section F, Structural biology and crystallization communications · 2013Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein engineering approaches are often a combination of rational design and directed evolution using display technologies. Here, we test "loop grafting," a rational design method, on three-finger fold proteins. These small reticulated proteins have exceptional affinity and specificity for their diverse molecular targets, display protease-resistance, and are highly stable and poorly immunogenic. The wealth of structural knowledge makes them good candidates for protein engineering of new functionality. Our goal is to enhance the efficacy of these mini-proteins by modifying their pharmacological properties in order to extend their use in imaging, diagnostics and therapeutic applications. Using the interaction of three-finger fold toxins with muscarinic and adrenergic receptors as a model, chimeric toxins have been engineered by substituting loops on toxin MT7 by those from toxin MT1. The pharmacological impact of these grafts was examined using binding experiments on muscarinic receptors M1 and M4 and on the α(1A)-adrenoceptor. Some of the designed chimeric proteins have impressive gain of function on certain receptor subtypes achieving an original selectivity profile with high affinity for muscarinic receptor M1 and α(1A)-adrenoceptor. Structure-function analysis supported by crystallographic data for MT1 and two chimeras permits a molecular based interpretation of these gains and details the merits of this protein engineering technique. The results obtained shed light on how loop permutation can be used to design new three-finger proteins with original pharmacological profiles.
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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.