title: The η-class carbonic anhydrases as drug targets for antimalarial agents.
abstract: BACKGROUND
  The η-class of carbonic anhydrases (CAs, EC 4.2.1.1) was recently discovered as the sixth genetic family of this metalloenzyme superfamily, and seems to be present only in various Plasmodium species, the malaria-provoking pathogens. The present review through detailed biochemical, kinetic and phylogenetic studies afford a clear view regarding the differences between η- and the other CA families.
  
  
  METHODS
  In this review, the authors underlined as the η-CAs, like α-, γ- and δ-class enzymes, have the Zn(II) ion coordinated by three histidine residues and a water molecule. They seem to be more closely related to the α-CAs, but there are notable differences between them, such as the lack of the proton shuttle residue (His64) and gatekeeper residues, Glu106 and Thr199 in the η-CAs, which are conserved in all α-CAs.
  
  
  CONCLUSIONS
  Plasmodium falciparum η-CA showed a moderate but significant activity for the CO2 hydration reaction, with a kcat of 1.4 × 10(5)s(-1) and a kcat/Km of 5.4 × 10(6) M(-1) × s(-1). Several inhibition studies with anions and sulfonamides/sulfamates, allowed the identification of interesting lead compounds. The discovery of η-CA-specific inhibitors may lead to novel such agents with a new mechanism of action.
authors.affiliation: Università degli Studi di Firenze, Dipartmento di Chimica Ugo Schiff , Via della Lastruccia 3, Rm. 188, 50019 - Sesto Fiorentino (Florence) , Italy.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
authors.forename: Clemente
authors.initials: C
authors.lastname: Capasso
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000737:chemistry / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology; D058990:Molecular Targeted Therapy; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology
chemical_list: D000962:Antimalarials; D002257:Carbonic Anhydrase Inhibitors; D002256:Carbonic Anhydrases
keywords: anion inhibitor; antimalarials; carbonic anhydrase; drug target; sulfonamide; η-class enzyme