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Cited by 1,022Enzyme function and inhibitionPhysical Organic Chemistry and Reaction KineticsEnzyme Structure and Function

The DOI matches its Crossref record; 206 of the 212 references it cites were found in a registry or an index.

Structure and mechanism of carbonic anhydrase

Lindskog, Sven·1997·Pharmacology & Therapeutics
DOI 10.1016/s0163-7258(96)00198-2
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Abstract

Carbonic anhydrase (CA; carbonate hydro-lyase, EC 4.2.1.1) is a zinc-containing enzyme that catalyzes the reversible hydration of carbon dioxide: CO2+ H2O<-->HCO3(-)+H+. The enzyme is the target for drugs, such as acetazolamide, methazolamide, and dichlorphenamide, for the treatment of glaucoma. There are three evolutionarily unrelated CA families, designated alpha, beta, and gamma. All known CAs from the animal kingdom are of the alpha type. There are seven mammalian CA isozymes with different tissue distributions and intracellular locations, CA I-VII. Crystal structures of human CA I and II, bovine CA III, and murine CA V have been determined. All of them have the same tertiary fold, with a central 10-stranded beta-sheet as the dominating secondary structure element. The zinc ion is located in a cone-shaped cavity and coordinated to three histidyl residues and a solvent molecule. Inhibitors bind at or near the metal center guided by a hydrogen-bonded system comprising Glu-106 and Thr-199. The catalytic mechanism of CA II has been studied in particular detail. It involves an attack of zinc-bound OH- on a CO2 molecule loosely bound in a hydrophobic pocket. The resulting zinc-coordinated HCO3- ion is displaced from the metal ion by H2O. The rate-limiting step is an intramolecular proton transfer from the zinc-bound water molecule to His-64, which serves as a proton shuttle between the metal center and buffer molecules in the reaction medium.

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Citations

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Research works printed but not linked: 5

  1. Campbell, 1974, A study of the histidine residues of human carbonic anhydrase B using 270 MHz proton magnetic resonance, J. Mol. Biol., 90, 469, 10.1016/0022-2836(74)90229-0 · DOI
  2. Kumar, 1989, Crystal structure of carbonic anhydrase II from erythrocyte of indian buffalo (Bubalus bubalis), Curr. Sci., 58, 344
  3. Lindskog, 1982, Carbonic anhydrase, Vol. 4, 115
  4. Lindskog, 1971, Carbonic anhydrase, Vol. 5, 587
  5. Wagner, 1991, A human carbonic anhydrase I deficiency appears to be caused by a destabilizing amino acid substitution (246-Arg→His), Isozyme Bull., 24, 35

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Metadata

Authors
Lindskog, S.
Affiliations
Umeå University (SE)
Corresponding author
Lindskog, Sven
Venue
Pharmacology & Therapeutics
Publisher
Elsevier BV
Published
1997-01
Volume
74
Issue
1
Pages
1-20
ISSN
0163-7258 (ISSN-L)
DOI
10.1016/s0163-7258(96)00198-2
OpenAlex
W2035046825
Cited by
1,022
References
212
Citations by year
2026: 38 · 2025: 52 · 2024: 63 · 2023: 50 · 2022: 49 · 2021: 49 · 2020: 34 · 2019: 45 · 2018: 46 · 2017: 38 · 2016: 42 · 2015: 40 · 2014: 41 · 2013: 47 · 2012: 48
FWCI
1.07
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Pharmacology & Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme function and inhibition
  • Physical Sciences › Chemistry › Organic Chemistry › Physical Organic Chemistry and Reaction Kinetics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
Keywords
carbonic anhydrase, zinc metalloenzyme, CO2 hydration, bicarbonate, catalytic mechanism, isozymes, crystal structure, acetazolamide, carbonic anhydrase inhibitors, glaucoma, proton transfer, histidine residues
MeSH terms
Animals, Carbonic Anhydrases, Catalysis, Humans, Protein Conformation, Structure-Activity Relationship

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