Abstract

We report the biochemical and structural characterisation of a beta-carbonic anhydrase (β-CA) from Trichomonas 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 (α, β, γ, δ, ζ, η, θ, and ι); humans express only α-CAs, whereas many clinically significant pathogens express only β- and/or γ-CAs. For this reason, the latter two groups of CAs are promising biomedical targets for novel antiinfective agents. The β-CA from T. vaginalis (TvaCA1) was recombinantly produced and biochemically characterised. The crystal structure was determined, revealing the canonical dimeric fold of β-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.

摘要

我们报告了从毛滴虫，一种单细胞的寄生虫，负责世界领先的性传播感染之一，滴虫的β-碳酸酐酶（β-CA）的生化和结构表征。CA是普遍存在的金属酶，属于八个进化发散基团（α，β，γ，δ，ζ，η，θ和ι）；人类仅表达α-CA，而许多具有临床意义的病原体仅表达β-和/或γ-CA。因此，后两组CA有望成为新型抗感染药的生物医学靶标。阴道锥虫的β-CA（TvaCA1）被重组生产并进行生化鉴定。确定了晶体结构，揭示了β-CAs的典型二聚折叠和酶活性位点的主要特征。与人类CA酶的活性位点的比较显示出显着的差异，该差异可用于设计相对于人类对原生动物酶具有选择性的抑制剂。