ArticleThe Journal of biological chemistry2011
Ensemble perspective for catalytic promiscuity: calorimetric analysis of the active site conformational landscape of a detoxification enzyme.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- Ligand binding Pro-miscuity of acylpeptide hydrolase, structural analysis of a detoxifying serine hydrolase.Protein science : a publication of the Protein Society · 2025Article
- The Ensemble Basis of Allostery and Function: Insights from Models of Local Unfolding.Journal of molecular biology · 2025Review
- Research on the GST gene family in Salix lindleyana reveals Trp162 and Pro202 as key amino acids controlling the release rate of GS-X.BMC plant biology · 2025Article
- Reversibility and Low Commitment to Forward Catalysis in the Conjugation of Lipid Alkenals by Glutathione Transferase A4-4.Biomolecules · 2023Article
- Molecular and thermodynamic mechanisms for protein adaptation.European biophysics journal : EBJ · 2022Review
- Analytical and functional aspects of protein-ligand interactions: Beyond induced fit and conformational selection.Archives of biochemistry and biophysics · 2021Review
- Mechanisms of promiscuity among drug metabolizing enzymes and drug transporters.The FEBS journal · 2020Review
- Evolutionary repurposing of a sulfatase: A new Michaelis complex leads to efficient transition state charge offset.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Plant glutathione transferase-mediated stress tolerance: functions and biotechnological applications.Plant cell reports · 2017Review
- Biological messiness vs. biological genius: Mechanistic aspects and roles of protein promiscuity.The Journal of steroid biochemistry and molecular biology · 2015Review
- Enzyme promiscuity: engine of evolutionary innovation.The Journal of biological chemistry · 2014Review
- Associations of GSTM1*0 and GSTA1*A genotypes with the risk of cardiovascular death among hemodialyses patients.BMC nephrology · 2014Article
- The evolutionary origins of detoxifying enzymes: the mammalian serum paraoxonases (PONs) relate to bacterial homoserine lactonases.The Journal of biological chemistry · 2013Article
- Enzymatic detoxication, conformational selection, and the role of molten globule active sites.The Journal of biological chemistry · 2013Article
- Escape from Adaptive Conflict follows from weak functional trade-offs and mutational robustness.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Evolutionary dynamics on protein bi-stability landscapes can potentially resolve adaptive conflicts.PLoS computational biology · 2012Article
- A glutathione transferase from Agrobacterium tumefaciens reveals a novel class of bacterial GST superfamily.PloS one · 2012Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Enzymological paradigms have shifted recently to acknowledge the biological importance of catalytic promiscuity. However, catalytic promiscuity is a poorly understood property, and no thermodynamic treatment has described the conformational landscape of promiscuous versus substrate-specific enzymes. Here, two structurally similar glutathione transferase (GST, glutathione S-transferase) isoforms with high specificity or high promiscuity are compared. Differential scanning calorimetry (DSC) indicates a reversible low temperature transition for the promiscuous GSTA1-1 that is not observed with substrate-specific GSTA4-4. This transition is assigned to rearrangement of the C terminus at the active site of GSTA1-1 based on the effects of ligands and mutations. Near-UV and far-UV circular dichroism indicate that this transition is due to repacking of tertiary contacts with the remainder of the subunit, rather than "unfolding" of the C terminus per se. Analysis of the DSC data using a modified Landau theory indicates that the local conformational landscape of the active site of GSTA1-1 is smooth, with barrierless transitions between states. The partition function of the C-terminal states is a broad unimodal distribution at all temperatures within this DSC transition. In contrast, the remainder of the GSTA1-1 subunit and the GSTA4-4 protein exhibit folded and unfolded macrostates with a significant energy barrier separating them. Their partition function includes a sharp unimodal distribution of states only at temperatures that yield either folded or unfolded macrostates. At intermediate temperatures the partition function includes a bimodal distribution. The barrierless rearrangement of the GSTA1-1 active site within a local smooth energy landscape suggests a thermodynamic basis for catalytic promiscuity.
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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.