Format

Send to

Choose Destination
Bioorg Med Chem Lett. 2015 Sep 1;25(17):3550-5. doi: 10.1016/j.bmcl.2015.06.079. Epub 2015 Jul 3.

Sulfonamide inhibition studies of the γ-carbonic anhydrase from the Antarctic bacterium Pseudoalteromonas haloplanktis.

Author information

1
Università degli Studi di Firenze, Dipartimento Di Chimica, Laboratorio di Chimica Bioinorganica, 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
Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 81, Napoli, Italy; Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche, Polo Scientifico, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
4
Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 81, Napoli, Italy. Electronic address: clemente.capasso@ibbr.cnr.it.
5
Università degli Studi di Firenze, Dipartimento Di Chimica, Laboratorio di Chimica Bioinorganica, Polo Scientifico, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy; Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche, Polo Scientifico, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy. Electronic address: claudiu.supuran@unifi.it.

Abstract

The Antarctic bacterium Pseudoalteromonas haloplanktis encodes for a γ-class carbonic anhydrase (CA, EC 4.2.1.1), which was cloned, purified and characterized. The enzyme (PhaCAγ) has a good catalytic activity for the physiologic reaction of CO2 hydration to bicarbonate and protons, with a k(cat) of 1.4×10(5) s(-1) and a k(cat)/K(m) of 1.9×10(6) M(-1)×s(-1). A series of sulfonamides and a sulfamate were investigated as inhibitors of the new enzyme. Methazolamide and indisulam showed the best inhibitory properties (K(I)s of 86.7-94.7 nM). This contribution shed new light on γ-CAs inhibition profiles with a relevant class of pharmacologic agents.

KEYWORDS:

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

PMID:
26174556
DOI:
10.1016/j.bmcl.2015.06.079
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center