ArticleJournal of the American Chemical Society2009
Elucidation of the proton transport mechanism in human carbonic anhydrase II.
Article in Journal of the American Chemical Society, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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
47 citing papers in PubMed.
- Proton Transport as a Missing Design Variable in Immobilized Enzyme Catalysis.Chembiochem : a European journal of chemical biology · 2026Article
- Benchmark Study for Calculations of pKa Values of Metal Ligands in Proteins.Journal of chemical theory and computation · 2026Article
- Primitive Basic Amino Acids Promote Mineral-Catalyzed Electrochemical Reduction of HThe journal of physical chemistry. C, Nanomaterials and interfaces · 2026Article
- COACS applied materials & interfaces · 2026Article
- Conformational flexibility of His200 enables catalytic activity in the T200H mutant of carbonic anhydrase II.Molecules and cells · 2025Article
- Molecular Principles of Proton-Coupled Quinone Reduction in the Membrane-Bound Superoxide Oxidase.Journal of the American Chemical Society · 2025Article
- XFEL structure of carbonic anhydrase II: a comparative study of XFEL, NMR, X-ray and neutron structures.Acta crystallographica. Section D, Structural biology · 2024Article
- Review
- Article
- Review
- Conformational Change of H64 and Substrate Transportation: Insight Into a Full Picture of Enzymatic Hydration of COFrontiers in chemistry · 2021Article
- Article
- Mechanism of Action of Non-Synonymous Single Nucleotide Variations Associated withMolecules (Basel, Switzerland) · 2019Article
- Kinetic Study of COBiomimetics (Basel, Switzerland) · 2019Article
- Kinetic study of catalytic CORoyal Society open science · 2019Article
- The Crystal Structure of a hCA VII Variant Provides Insights into the Molecular Determinants Responsible for Its Catalytic Behavior.International journal of molecular sciences · 2018Article
- Crystallography and Its Impact on Carbonic Anhydrase Research.International journal of medicinal chemistry · 2018Review
- Analysis of Phosphoryl-Transfer Enzymes with QM/MM Free Energy Simulations.Methods in enzymology · 2018Article
- Metal Ion Modeling Using Classical Mechanics.Chemical reviews · 2017Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
Human carbonic anhydrase II (HCA II) is one of the fastest known enzymes, which utilizes a rate-limiting proton transport (PT) step in its enzymatic reaction. To evaluate the PT event at an atomistic level, the multistate empirical valence bond (MS-EVB) method has been utilized in this work. It is observed that the PT event in HCA II exploits a transient active site water cluster to transport the excess proton between the catalytic zinc-bound water/hydroxide and the proton shuttling residue, His64. This PT event is found to be dependent on the enzyme's ability to form and stabilize the active site water cluster in addition to its ability to orient His64 in a favorable conformation. Evaluation of the PT free energy barrier for different orientations of His64 reveals this residue's vital role as a proton transporter and elucidates its direct effect on the barrier to PT through the active site water. It is suggested that the rate-limiting step oscillates between the active site water PT event to His64 and the de/protonation of His64 depending on the exogenous buffer concentration and the orientation of His64. In the absence of a PT acceptor/donor at position 64, it is found that the excess proton will utilize one of three distinct paths to enter/leave the active site. This latter result not only allows for an increased understanding of how enzymes capitalize on the protein/solvent interface to guide excess protons to/from areas of interest, it also provides valuable insight into the chemical rescue experiments on HCA II mutants.
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.