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Bioorg Med Chem Lett. 2016 Feb 15;26(4):1253-9. doi: 10.1016/j.bmcl.2016.01.023. Epub 2016 Jan 11.

Sulfonamide inhibition studies of the γ-carbonic anhydrase from the Antarctic bacterium Colwellia psychrerythraea.

Author information

1
Università degli Studi di Firenze, Dipartimento Di Chimica, Laboratorio di ChimicaBioinorganica, Polo Scientifico, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
2
Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 81, Napoli, Italy.
3
Università degli Studi di Firenze, Dipartimento Di Chimica, Laboratorio di ChimicaBioinorganica, Polo Scientifico, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy; Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 81, Napoli, Italy.
4
Department of Chemistry, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia; Advanced Materials Research Chair, Chemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
5
Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 81, Napoli, Italy. Electronic address: clemente.capasso@ibbr.cnr.it.
6
Università degli Studi di Firenze, Dipartimento Di Chimica, Laboratorio di ChimicaBioinorganica, Polo Scientifico, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy; Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy. Electronic address: claudiu.supuran@unifi.it.

Abstract

The Antarctic bacterium Colwellia psychrerythraea encodes for a γ-class carbonic anhydrase (CA, EC 4.2.1.1), which was cloned, purified and characterized. The enzyme (CpsCAγ) has a moderate catalytic activity for the physiologic reaction of CO2 hydration to bicarbonate and protons, with a k(cat) 6.0×10(5) s(-1) and a k(cat)/K(m) of 4.7×10(6) M(-1) s(-1). A series of sulfonamides and a sulfamate were investigated as inhibitors of the new enzyme. The best inhibitor was metanilamide (K(I) of 83.5 nM) followed by indisulam, valdecoxib, celecoxib, sulthiame and hydrochlorothiazide (K(I)s ranging between 343 and 491 nM). Acetazolamide, methazolamide as well as other aromatic/heterocyclic derivatives showed inhibition constants between 502 and 7660 nM. The present study may shed some more light regarding the role that γ-CAs play in the life cycle of psychrophilic bacteria as the Antarctic one investigated here, by allowing the identification of inhibitors which may be useful as pharmacologic tools.

KEYWORDS:

Antarctic carbonic anhydrase; Carbonic anhydrase; Cold adaptation; Cold enzymes; Hydratase activity; Inhibitors; Metalloenzymes; Psychrophiles; Sulfonamide

PMID:
26832216
DOI:
10.1016/j.bmcl.2016.01.023
[Indexed for MEDLINE]

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