ArticleIUCrJ2014
Structural insight into activity enhancement and inhibition of H64A carbonic anhydrase II by imidazoles.
Article in IUCrJ, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 34 citations in OpenAlex.
- Carbonic Anhydrase Activators for Neurodegeneration: An Overview.Molecules (Basel, Switzerland) · 2022Review
- Review
- New Histamine-Related Five-Membered N-Heterocycle Derivatives as Carbonic Anhydrase I Activators.Molecules (Basel, Switzerland) · 2022Article
- Amine- and Amino Acid-Based Compounds as Carbonic Anhydrase Activators.Molecules (Basel, Switzerland) · 2021Review
- Conformational Change of H64 and Substrate Transportation: Insight Into a Full Picture of Enzymatic Hydration of COFrontiers in chemistry · 2021Article
- Human carbonic anhydrases and post-translational modifications: a hidden world possibly affecting protein properties and functions.Journal of enzyme inhibition and medicinal chemistry · 2020Review
- Article
- Carbonic anhydrase modification for carbon management.Environmental science and pollution research international · 2020Article
- Sulfonamide-Based Azaheterocyclic Schiff Base Derivatives as Potential Carbonic Anhydrase Inhibitors: Synthesis, Cytotoxicity, and Enzyme Inhibitory Kinetics.BioMed research international · 2020Article
- Crystal Structure of Carbonic Anhydrase II in Complex with an Activating Ligand: Implications in Neuronal Function.Molecular neurobiology · 2018Article
- 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
- Polyamines and α-Carbonic Anhydrases.Molecules (Basel, Switzerland) · 2016Review
- Article
- Coupling Protein Dynamics with Proton Transport in Human Carbonic Anhydrase II.The journal of physical chemistry. B · 2016Article
- Non-Classical Inhibition of Carbonic Anhydrase.International journal of molecular sciences · 2016Review
- Carbon Dioxide "Trapped" in a β-Carbonic Anhydrase.Biochemistry · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Human carbonic anhydrases (CAs) are zinc metalloenzymes that catalyze the hydration and dehydration of CO2 and HCO3 (-), respectively. The reaction follows a ping-pong mechanism, in which the rate-limiting step is the transfer of a proton from the zinc-bound solvent (OH(-)/H2O) in/out of the active site via His64, which is widely believed to be the proton-shuttling residue. The decreased catalytic activity (∼20-fold lower with respect to the wild type) of a variant of CA II in which His64 is replaced with Ala (H64A CA II) can be enhanced by exogenous proton donors/acceptors, usually derivatives of imidazoles and pyridines, to almost the wild-type level. X-ray crystal structures of H64A CA II in complex with four imidazole derivatives (imidazole, 1--methylimidazole, 2--methylimidazole and 4-methylimidazole) have been determined and reveal multiple binding sites. Two of these imidazole binding sites have been identified that mimic the positions of the 'in' and 'out' rotamers of His64 in wild-type CA II, while another directly inhibits catalysis by displacing the zinc-bound solvent. The data presented here not only corroborate the importance of the imidazole side chain of His64 in proton transfer during CA catalysis, but also provide a complete structural understanding of the mechanism by which imidazoles enhance (and inhibit when used at higher concentrations) the activity of H64A CA II.
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