Format

Send to

Choose Destination
Bioorg Med Chem. 2015 Apr 15;23(8):1728-34. doi: 10.1016/j.bmc.2015.02.045. Epub 2015 Mar 4.

Sulfonamide inhibition studies of the γ-carbonic anhydrase from the Antarctic cyanobacterium Nostoc commune.

Author information

1
Università degliStudi di Firenze, Dipartimento Di Chimica, Laboratorio di ChimicaBioinorganica, Polo Scientifico, Via della Lastruccia3, 50019 Sesto Fiorentino, Florence, Italy.
2
Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 81, Napoli, Italy.
3
Università degliStudi di Firenze, Dipartimento Di Chimica, Laboratorio di ChimicaBioinorganica, Polo Scientifico, Via della Lastruccia3, 50019 Sesto Fiorentino, Florence, Italy; Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 81, Napoli, Italy.
4
Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 81, Napoli, Italy. Electronic address: clemente.capasso@ibbr.cnr.it.
5
Università degliStudi di Firenze, Dipartimento Di Chimica, Laboratorio di ChimicaBioinorganica, Polo Scientifico, Via della Lastruccia3, 50019 Sesto Fiorentino, Florence, Italy; Università degliStudi di Firenze, DipartimentoNeurofarba, Sezione di ScienzeFarmaceutiche, Polo Scientifico, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy. Electronic address: claudiu.supuran@unifi.it.

Abstract

A carbonic anhydrase (CA, EC 4.2.1.1) belonging to the γ-class has been cloned, purified and characterized from the Antarctic cyanobacterium Nostoc commune. The enzyme showed a good catalytic activity for the physiologic reaction (hydration of carbon dioxide to bicarbonate and a proton) with the following kinetic parameters, kcat of 9.5×10(5)s(-1) and kcat/KM of 8.3×10(7)M(-1)s(-1), being the γ-CA with the highest catalytic activity described so far. A range of aromatic/heterocyclic sulfonamides and one sulfamate were investigated as inhibitors of the new enzyme, denominated here NcoCA. The best NcoCA inhibitors were some sulfonylated sulfanilamide derivatives possessing elongated molecules, aminobenzolamide, acetazolamide, benzolamide, dorzolamide, brinzolamide and topiramate, which showed inhibition constants in the range of 40.3-92.3nM. As 1,5-bisphosphate carboxylase/oxygenase (RubisCO) and γ-CAs are closely associated in carboxysomes of cyanobacteria for enhancing the affinity of RubisCO for CO2 and the efficiency of photosynthesis, investigation of this new enzyme and its affinity for modulators of its activity may bring new insights in these crucial processes.

KEYWORDS:

Antarctic carbonic anhydrase; Carbonic anhydrase; Cyanobacteria; Hydratase activity; Metalloenzymes

PMID:
25773015
DOI:
10.1016/j.bmc.2015.02.045
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center