Carbonic anhydrase inhibitors. Inhibition of the beta-class enzyme from the methanoarchaeon Methanobacterium thermoautotrophicum (Cab) with anions
Abstract
The first inhibition study of the beta-class carbonic anhydrase (CA, EC 4.2.1.1) from the methanoarchaeon Methanobacterium thermoautotrophicum (Cab) with anions is reported here. Inhibition data of the alpha-class human isozymes hCA I and hCA II (cytosolic) as well as the membrane-bound isozyme hCA IV and the gamma-class enzyme from another archaeon, Methanosarcina thermophila (Cam) with a large number of anionic species such as halides, pseudohalides, bicarbonate, carbonate, nitrate, nitrite, hydrosulfide, bisulfite, sulfate, etc., are also provided for comparison. The best Cab anion inhibitors were thiocyanate and hydrogen sulfide, with inhibition constants in the range of 0.52-0.70 mM, whereas cyanate, iodide, carbonate, and nitrate were weaker inhibitors (Ki's in the range of 7.8-13.2 mM). Fluoride, chloride, and sulfate do not inhibit this enzyme appreciably, whereas the CA substrate bicarbonate, or other anions, such as bromide, nitrite, bisulfite, or sulfamate behave as weak inhibitors (Ki in the range of 40-45 mM). It is interesting to note that the metal poison, coordinating anions cyanide and azide are also rather weak Cab inhibitors (Ki in the range of 27-55 mM), whereas sulfamide is a very weak Cab inhibitor (Ki of 103 mM), although it strongly inhibits Cam (Ki of 70 microM). Surprisingly, phenylboronic and phenylarsonic acids, which have been investigated for the inhibition of all these CAs for the first time, showed very weak activity against the alpha-CA isozymes, but were effective Cab and Cam inhibitors. The best Cab inhibitors were just these two compounds (Ki's of 0.20-0.33 mM), whereas the best Cam inhibitor was sulfamic acid (Ki of 96 nM). These major differences of behavior between the diverse CAs investigated here toward anion inhibitors can be difficultly explained considering the convergent evolution of so diverse enzymes for the binding and turnover of small molecules such as carbon dioxide and anions.
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The affinity of nitrite itself for CA is also likely to be low based on its measured inhibition constant (KI of about 40 mM).
“The affinity of nitrite itself for CA is also likely to be low based on its measured inhibition constant (KI of about 40 mM [106]) [103].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [106]
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- Authors
- Innocenti, A., Zimmerman, S., Ferry, J., Scozzafava, A., & Supuran, C.
- Affiliations
- University of Florence (IT)
- Pennsylvania State University (US)
- Corresponding author
- Supuran, Claudiu
- Venue
- Bioorganic & Medicinal Chemistry Letters
- Publisher
- Elsevier BV
- Published
- 2004-09
- Volume
- 14
- Issue
- 17
- Pages
- 4563-4567
- ISSN
- 0960-894X (ISSN-L)
- OpenAlex
- W2083659388
- Cited by
- 50
- References
- 36
- Citations by year
- 2023: 1 · 2022: 4 · 2021: 2 · 2020: 3 · 2018: 2 · 2017: 2 · 2015: 8 · 2014: 2 · 2013: 4
- FWCI
- 1.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Bioorganic & Medicinal Chemistry Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Aeronautics and Space Administration
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM044661, GM 44661)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme function and inhibition
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Reaction Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- carbonic anhydrase, Methanobacterium thermoautotrophicum, enzyme inhibition, thiocyanate, hydrogen sulfide, cyanide, azide, sulfamides, phenylboronic acid, phenylarsonic acid, sulfamic acid, Methanosarcina thermophila, bicarbonate, halides, pseudohalides, sulfite
- MeSH terms
- Anions, Carbonic Anhydrase Inhibitors, Humans, Isoenzymes, Methanobacterium, Carbonic Anhydrase I
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