ArticleJournal of the American Chemical Society2023
Second-Shell Residues Contribute to Catalysis by Predominately Preorganizing the Apo State in PafA.
Article in Journal of the American Chemical Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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
11 citing papers in PubMed, 13 citations in OpenAlex.
- Engineering of fructose-6-phosphate aldolase for one-carbon conversion to mannitol in a designed biotransformation system.Synthetic and systems biotechnology · 2026Article
- Creating highly active fluoroacetate dehalogenases via gate-based synergetic chain design.Nature communications · 2026Article
- Force fields matter in DNA polProtein science : a publication of the Protein Society · 2026Article
- Approaches for regulating enzyme activities: Recent advances in experiment and computation.Current opinion in structural biology · 2025Review
- Computational studies on the functional and structural impact of pathogenic mutations in enzymes.Protein science : a publication of the Protein Society · 2025Review
- Enhancing Bacillus cereus antibacterial ability through improved cofactor supply.Microbial cell factories · 2025Article
- Long-Range Electrostatics in Serine Proteases: Machine Learning-Driven Reaction Sampling Yields Insights for Enzyme Design.Journal of chemical information and modeling · 2025Article
- Correlating enzymatic reactivity for different substrates using transferable data-driven collective variables.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- CHARMM at 45: Enhancements in Accessibility, Functionality, and Speed.The journal of physical chemistry. B · 2024Review
- Harnessing generative AI to decode enzyme catalysis and evolution for enhanced engineering.National science review · 2023Review
- Harnessing Generative AI to Decode Enzyme Catalysis and Evolution for Enhanced Engineering.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Residues beyond the first coordination shell are often observed to make considerable cumulative contributions in enzymes. Due to typically indirect perturbations of multiple physicochemical properties of the active site, however, their individual and specific roles in enzyme catalysis and disease-causing mutations remain difficult to predict and understand at the molecular level. Here we analyze the contributions of several second-shell residues in phosphate-irrepressible alkaline phosphatase of flavobacterium (PafA), a representative system as one of the most efficient enzymes. By adopting a multifaceted approach that integrates quantum-mechanical/molecular-mechanical free energy computations, molecular-mechanical molecular dynamics simulations, and density functional theory cluster model calculations, we probe the rate-limiting phosphoryl transfer step and structural properties of all relevant enzyme states. In combination with available experimental data, our computational results show that mutations of the studied second-shell residues impact catalytic efficiency mainly by perturbation of the apo state and therefore substrate binding, while they do not affect the ground state or alter the nature of phosphoryl transfer transition state significantly. Several second-shell mutations also modulate the active site hydration level, which in turn influences the energetics of phosphoryl transfer. These mechanistic insights also help inform strategies that may improve the efficiency of enzyme design and engineering by going beyond the current focus on the first coordination shell.
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.