ArticleProceedings of the National Academy of Sciences of the United States of America2022
Temperature-sensitive contacts in disordered loops tune enzyme I activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Integrating NMR and contact-response analysis reveals the allosteric network driving domain closure in Enzyme I.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Constrained diffusion-enabled construction of a highly expressed and robust peptide asparaginyl ligase.Chemical science · 2026Article
- Loop engineering of AtCas9 for effective and broad genome editing.Cell insight · 2025Article
- Dynamically Interacting Protein Networks Provide a Mechanism to Overcome the Enormous Intrinsic Barrier to Orotidine 5'-Monophosphate Decarboxylation.ACS central science · 2025Article
- Thermal adaptation of extremozymes: Temperature-sensitive contact analysis of serine proteases.Biophysical journal · 2025Article
- Anti-Hangover and Hepatoprotective Effects of the Leaf Extract ofPharmaceuticals (Basel, Switzerland) · 2025Article
- Identification of Scaffold Specific Energy Transfer Networks in the Enthalpic Activation of Orotidine 5'-Monophosphate Decarboxylase.bioRxiv : the preprint server for biology · 2025Article
- Illuminating Protein Allostery by Chemically Accurate Contact Response Analysis (ChACRA).Journal of chemical theory and computation · 2024Article
- Identification of the Thermal Activation Network in Human 15-Lipoxygenase-2: Divergence from Plant Orthologs and Its Relationship to Hydrogen Tunneling Activation Barriers.ACS catalysis · 2024Article
- Temperature sensitive contact modes allosterically gate TRPV3.PLoS computational biology · 2023Article
- Temperature as a modulator of allosteric motions and crosstalk in mesophilic and thermophilic enzymes.Frontiers in molecular biosciences · 2023Review
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Authors and funding
4 authors.
Funding
Abstract
Homologous enzymes with identical folds often exhibit different thermal and kinetic behaviors. Understanding how an enzyme sequence encodes catalytic activity at functionally optimal temperatures is a fundamental problem in biophysics. Recently it was shown that the residues that tune catalytic activities of thermophilic/mesophilic variants of the C-terminal domain of bacterial enzyme I (EIC) are largely localized within disordered loops, offering a model system with which to investigate this phenomenon. In this work, we use molecular dynamics simulations and mutagenesis experiments to reveal a mechanism of sequence-dependent activity tuning of EIC homologs. We find that a network of contacts in the catalytic loops is particularly sensitive to changes in temperature, with some contacts exhibiting distinct linear or nonlinear temperature-dependent trends. Moreover, these trends define structurally clustered dynamical modes and can distinguish regions that tend toward order or disorder at higher temperatures. Assaying several thermophilic EIC mutants, we show that complementary mesophilic mutations to the most temperature-sensitive positions exhibit the most enhanced activity, while mutations to relatively temperature insensitive positions exhibit the least enhanced activities. These results provide a mechanistic explanation of sequence-dependent temperature tuning and offer a computational method for rational enzyme modification.
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