Biochemical and structural characterisation of a protozoan beta-carbonic anhydrase fromTrichomonas vaginalis

We report the biochemical and structural characterisation of a beta-carbonic anhydrase (beta-CA) fromTrichomonas vaginalis, a unicellular parasite responsible for one of the world's leading sexually transmitted infections, trichomoniasis. CAs are ubiquitous metalloenzymes belonging to eight evolutionarily divergent groups (alpha, beta, gamma, delta, zeta, eta, theta, and iota); humans express only alpha-CAs, whereas many clinically significant pathogens express only beta- and/or gamma-CAs. For this reason, the latter two groups of CAs are promising biomedical targets for novel antiinfective agents. The beta-CA fromT. vaginalis(TvaCA1) was recombinantly produced and biochemically characterised. The crystal structure was determined, revealing the canonical dimeric fold of beta-CAs and the main features of the enzyme active site. The comparison with the active site of human CA enzymes revealed significant differences that can be exploited for the design of inhibitors selective for the protozoan enzyme with respect to the human ones.