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Bioorg Med Chem Lett. 2014 Sep 15;24(18):4389-4396. doi: 10.1016/j.bmcl.2014.08.015. Epub 2014 Aug 12.

Discovery of a new family of carbonic anhydrases in the malaria pathogen Plasmodium falciparum--the η-carbonic anhydrases.

Author information

1
Istituto di Bioscienze e Biorisorse (IBBR)-CNR, via P. Castellino 111, 80131 Napoli, Italy.
2
Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy.
3
Eskitis Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia.
4
Istituto di Bioscienze e Biorisorse (IBBR)-CNR, via P. Castellino 111, 80131 Napoli, Italy. Electronic address: c.capasso@ibp.cnr.it.
5
Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy; Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche, Polo Scientifico, Sesto Fiorentino, Firenze, Italy. Electronic address: claudiu.supuran@unifi.it.

Abstract

The genome of the protozoan parasite Plasmodium falciparum, the causative agent of the most lethal type of human malaria, contains a single gene annotated as encoding a carbonic anhydrase (CAs, EC 4.2.1.1) thought to belong to the α-class, PfCA. Here we demonstrate the kinetic properties of PfCA for the CO2 hydration reaction, as well as an inhibition study of this enzyme with inorganic and complex anions and other molecules known to interact with zinc proteins, including sulfamide, sulfamic acid, and phenylboronic/arsonic acids, detecting several low micromolar inhibitors. A closer examination of the sequence of this and the CAs from other Plasmodium spp., as well as a phylogenetic analysis, revealed that these protozoa encode for a yet undisclosed, new genetic family of CAs termed the η-CA class. The main features of the η-CAs are described in this report.

KEYWORDS:

Anion; Carbonic anhydrase; Inhibitor; Plasmodium falciparum; η-CA-class enzyme

PMID:
25168745
DOI:
10.1016/j.bmcl.2014.08.015
[Indexed for MEDLINE]

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