ArticlePLoS computational biology2012
Rational engineering of enzyme allosteric regulation through sequence evolution analysis.
Article in PLoS computational biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed.
- Seven complete comparative maps of allosteric mutations in a protein family.Nature communications · 2026Article
- Single-Molecule DNA Tweezers Enable Programmable Control of Enzyme Activity via Arbitrary Molecular Cues.Angewandte Chemie (International ed. in English) · 2025Article
- Resistance to Allosteric Inhibitors.Journal of molecular biology · 2025Review
- The Role of α7-Nicotinic Acetylcholine Receptors in the Pathophysiology and Treatment of Parkinson's Disease.International journal of molecular sciences · 2025Review
- Visual hallucinations in Parkinson's disease: spotlight on central cholinergic dysfunction.Brain : a journal of neurology · 2025Review
- Allosteric modulation of Plasmodium falciparum Isoleucyl tRNA synthetase by South African natural compounds.PloS one · 2025Article
- A three-level regulatory mechanism of the aldo-keto reductase subfamily AKR12D.Nature communications · 2024Article
- Recent advances in targeting the "undruggable" proteins: from drug discovery to clinical trials.Signal transduction and targeted therapy · 2023Review
- Allosteric regulation and inhibition of protein kinases.Biochemical Society transactions · 2023Review
- Protein engineering for feedback resistance in 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase.Applied microbiology and biotechnology · 2022Article
- Identification and Inhibition of the Druggable Allosteric Site of SARS-CoV-2 NSP10/NSP16 Methyltransferase through Computational Approaches.Molecules (Basel, Switzerland) · 2022Article
- Targeting allosteric regulation of cancer metabolism.Nature chemical biology · 2022Review
- Known allosteric proteins have central roles in genetic disease.PLoS computational biology · 2022Article
- Activation of α7 nicotinic acetylcholine receptor ameliorates HIV-associated neurology and neuropathology.Brain : a journal of neurology · 2021Article
- ProteinLens: a web-based application for the analysis of allosteric signalling on atomistic graphs of biomolecules.Nucleic acids research · 2021Article
- An integrative approach to improving the biocatalytic reactions of whole cells expressing recombinant enzymes.World journal of microbiology & biotechnology · 2021Review
- Functional plasticity and evolutionary adaptation of allosteric regulation.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Recent advances suggest increased influence of selective pressure in allostery.Current opinion in structural biology · 2020Review
- Integrated Computational Approaches and Tools forAllosteric Drug Discovery.International journal of molecular sciences · 2020Review
- Allosteric inhibition explained through conformational ensembles sampling distinct "mixed" states.Computational and structural biotechnology journal · 2020Review
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Control of enzyme allosteric regulation is required to drive metabolic flux toward desired levels. Although the three-dimensional (3D) structures of many enzyme-ligand complexes are available, it is still difficult to rationally engineer an allosterically regulatable enzyme without decreasing its catalytic activity. Here, we describe an effective strategy to deregulate the allosteric inhibition of enzymes based on the molecular evolution and physicochemical characteristics of allosteric ligand-binding sites. We found that allosteric sites are evolutionarily variable and comprised of more hydrophobic residues than catalytic sites. We applied our findings to design mutations in selected target residues that deregulate the allosteric activity of fructose-1,6-bisphosphatase (FBPase). Specifically, charged amino acids at less conserved positions were substituted with hydrophobic or neutral amino acids with similar sizes. The engineered proteins successfully diminished the allosteric inhibition of E. coli FBPase without affecting its catalytic efficiency. We expect that our method will aid the rational design of enzyme allosteric regulation strategies and facilitate the control of metabolic flux.
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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.