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

作者：Del Prete, Sonia; Vullo, Daniela; Fisher, Gillian M.; Andrews, Katherine T.; Poulsen, Sally-Ann; Capasso, Clemente^*; Supuran, Claudiu T.

来源：Bioorganic & Medicinal Chemistry Letters, 2014, 24(18): 4389-4396.

DOI：10.1016/j.bmcl.2014.08.015

• Carbonic anhydrase
• eta-CA-class enzyme
• Anion
• Inhibitor
• Plasmodium falciparum

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 alpha-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 eta-CA class. The main features of the eta-CAs are described in this report.

• 出版日期2014-9-15