ArticleJournal of the American Chemical Society2016
Leaving Group Ability Observably Affects Transition State Structure in a Single Enzyme Active Site.
Article in Journal of the American Chemical Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 48 citations in OpenAlex.
- Structural basis for multi-subunit DNA-dependent RNA polymerase catalytic activity.Molecular cell · 2026Article
- Force fields matter in DNA polProtein science : a publication of the Protein Society · 2026Article
- CHARMM at 45: Enhancements in Accessibility, Functionality, and Speed.The journal of physical chemistry. B · 2024Review
- Second-Shell Residues Contribute to Catalysis by Predominately Preorganizing the Apo State in PafA.Journal of the American Chemical Society · 2023Article
- Factors That Determine the Variation of Equilibrium and Kinetic Properties of QM/MM Enzyme Simulations: QM Region, Conformation, and Boundary Condition.Journal of chemical theory and computation · 2022Article
- Monitoring protein conformational changes using fluorescent nanoantennas.Nature methods · 2022Article
- Enhanced-Sampling Simulations for the Estimation of Ligand Binding Kinetics: Current Status and Perspective.Frontiers in molecular biosciences · 2022Review
- Structures of an engineered phospholipase D with specificity for secondary alcohol transphosphatidylation: insights into plasticity of substrate binding and activation.The Biochemical journal · 2021Article
- What Does the Brønsted Slope Measure in the Phosphoryl Transfer Transition State?ACS catalysis · 2020Article
- Differences in the Nature of the Phosphoryl Transfer Transition State in Protein Phosphatase 1 and Alkaline Phosphatase: Insights from QM Cluster Models.The journal of physical chemistry. B · 2020Article
- Single-step Replacement of an Unreactive C-H Bond by a C-S Bond Using Polysulfide as the Direct Sulfur Source in Anaerobic Ergothioneine Biosynthesis.ACS catalysis · 2020Article
- Extensive free-energy simulations identify water as the base in nucleotide addition by DNA polymerase.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Two symmetric arginine residues play distinct roles inProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Mechanistic insights into the phosphoryl transfer reaction in cyclin-dependent kinase 2: A QM/MM study.PloS one · 2019Article
- Structural and mechanistic basis for preferential deadenylation of U6 snRNA by Usb1.Nucleic acids research · 2018Article
- Mechanistic Insights on Human Phosphoglucomutase Revealed by Transition Path Sampling and Molecular Dynamics Calculations.Chemistry (Weinheim an der Bergstrasse, Germany) · 2018Article
- Analysis of Phosphoryl-Transfer Enzymes with QM/MM Free Energy Simulations.Methods in enzymology · 2018Article
- Building a More Predictive Protein Force Field: A Systematic and Reproducible Route to AMBER-FB15.The journal of physical chemistry. B · 2017Article
- Regulation and Plasticity of Catalysis in Enzymes: Insights from Analysis of Mechanochemical Coupling in Myosin.Biochemistry · 2017Article
- Perspective: Quantum mechanical methods in biochemistry and biophysics.The Journal of chemical physics · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
A reaction's transition state (TS) structure plays a critical role in determining reactivity and has important implications for the design of catalysts, drugs, and other applications. Here, we explore TS structure in the enzyme alkaline phosphatase using hybrid Quantum Mechanics/Molecular Mechanics simulations. We find that minor perturbations to the substrate have major effects on TS structure and the way the enzyme stabilizes the TS. Substrates with good leaving groups (LGs) have little cleavage of the phosphorus-LG bond at the TS, while substrates with poor LGs have substantial cleavage of that bond. The results predict nonlinear free energy relationships for a single rate-determining step, and substantial differences in kinetic isotope effects for different substrates; both trends were observed in previous experimental studies, although the original interpretations differed from the present model. Moreover, due to different degrees of phosphorus-LG bond cleavage at the TS for different substrates, the LG is stabilized by different interactions at the TS: while a poor LG is directly stabilized by an active site zinc ion, a good LG is mainly stabilized by active site water molecules. Our results demonstrate the considerable plasticity of TS structure and stabilization in enzymes. Furthermore, perturbations to reactivity that probe TS structure experimentally (i.e., substituent effects) may substantially perturb the TS they aim to probe, and thus classical experimental approaches such as free energy relations should be interpreted with care.
Indexed as
Identifiers
What OpenQuestion holds
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.