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

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Del Prete, Sonia
Vullo, Daniela
Fisher, Gillian M
Andrews, Katherine T
Poulsen, Sally-Ann
Capasso, Clemente
Supuran, Claudiu T
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2014
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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 a-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 ?-CA class. The main features of the ?-CAs are described in this report.

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Bioorganic & Medicinal Chemistry Letters

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24

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18

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© 2014 Elsevier. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.

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Medicinal and biomolecular chemistry

Characterisation of biological macromolecules

Organic chemistry

Pharmacology and pharmaceutical sciences

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