MF7000856 Beta-carbonic anhydrase isoform I (TvaCA1) (Trichomonas vaginalis protozoan) 6y04 X-ray 2.48 Homodimer Trichomonas vaginalis 32515610 Urbański LJ, Di Fiore A, Azizi L, Hytönen VP, Kuuslahti M, Buonanno M, Monti SM, Angeli A, Zolfaghari Emameh R, Supuran CT, De Simone G, Parkkila S J Enzyme Inhib Med Chem 2020 1 35 1292-1299 We report the biochemical and structural characterisation of a beta-carbonic anhydrase (β-CA) from <i>Trichomonas vaginalis</i>, 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 <i>T. vaginalis</i> (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. GO:0004089 carbonate dehydratase activity GO:0008270 zinc ion binding 2 1 Homooligomeric enzymes Homodimeric enzymes All chains according to the most probable oligomerization state stored in PDBe were considered. A Carbonic anhydrase Trichomonas vaginalis A2ENQ8 1 182 100% MSQLELITSANQAFLEANPELTKLNKAPQRHIAIVTCMDTRLVNFAEDAIGVKRGEATVIKAAGNGIWTTGLSDIVVSLLVSIYELGVQEIFIMGHECCGMTHASTDSLGAQMLKSGIKPEDIEKFKSDLSKWVDDFKDPIDNIKNSVRCVRENPLIPKNIPIHGLLIHPDTGKVTTIINGY 182 secondary structure helix 2 18 secondary structure helix 39 43 secondary structure helix 45 50 secondary structure helix 73 85 secondary structure helix 105 116 secondary structure helix 119 135 secondary structure helix 139 153 secondary structure strand 32 36 secondary structure strand 57 61 secondary structure strand 90 96 secondary structure strand 163 168 secondary structure strand 175 179 pfam PF00484 Carbonic anhydrase 33 175 B Carbonic anhydrase Trichomonas vaginalis A2ENQ8 1 182 100% MSQLELITSANQAFLEANPELTKLNKAPQRHIAIVTCMDTRLVNFAEDAIGVKRGEATVIKAAGNGIWTTGLSDIVVSLLVSIYELGVQEIFIMGHECCGMTHASTDSLGAQMLKSGIKPEDIEKFKSDLSKWVDDFKDPIDNIKNSVRCVRENPLIPKNIPIHGLLIHPDTGKVTTIINGY 182 secondary structure helix 2 18 secondary structure helix 39 43 secondary structure helix 45 50 secondary structure helix 73 85 secondary structure helix 105 116 secondary structure helix 119 135 secondary structure helix 139 153 secondary structure strand 32 36 secondary structure strand 57 61 secondary structure strand 90 96 secondary structure strand 163 168 secondary structure strand 175 179 pfam PF00484 Carbonic anhydrase 33 175 Indirect evidence The full structure participates in mutual synergistic folding. Carbonic anhydrase The native carbonic anhydrase is dimeric in solution, in agreement with being a tightly associated dimer with a large, hydrophobic buried surface area. The extended β-sheet core consisting of ten β–strands is equally contributed by the two monomers, and the N-terminal helix of each monomer extends around the other monomer. Based on the highly intertwined structure, the monomeric form is most probably not a stable, independently folding unit. The two active sites are also located in clefts at the dimeric interface, further suggesting that dimer is the functional form (PMID:32515610). A N/A B N/A MF7000278 MF7000279 MF7000856 MF7000857 MF7000858 MF7000859