Figure 12.

Stabilization of region I in the closed conformation is mediated by Ca²⁺/Mg²⁺ in mitochondrial Prx1 from Leishmania species and by a water molecule in other AhpC/Prx1 subfamily members. a, sequence alignment of regions I, II, and III from the A-type interface as well as the C_p-loop from mitochondrial (Prx1m) and cytoplasmic (Prx1a) 2-Cys Prx from trypanosomatids with known crystallographic decamers. Note that residues involved in cation binding in LbPrx1m are highly conserved in the AhpC/Prx1 subfamily (red boxes). However, only the mitochondrial enzymes from Leishmania (black outlined area) conserve residues Cys-107, Lys-137, and Met-139 (green boxes) that render decamer stabilization of LbPrx1m highly sensitive to Ca²⁺ and Mg²⁺ ions (green circle). In other 2-Cys Prx, Lys-137 is replaced by neutral polar or hydrophobic residues or kept away from Asp-108 by residues bulkier than Cys-107. In most of the analyzed structures of AhpC/Prx1 subfamily members (blue circles), a water molecule mediates the link between the Asp-76 main chain and Asp-108, Ser-109, and eventually Ser-112 side chains. In a few cases, solvent molecules are not observed in the crystallographic structures due to the low resolution of data (open circles). Lb, L. braziliensis; Li, L. infantum; Lp, Leishmania panamensis; Ld, Leishmania donovani; La, L. amazonensis; Lm, Leishmania major; Tv, Trypanosoma vivax; Tb, Trypanosoma brucei; Tc, T. cruzi; Tco, Trypanosoma congolense; Ac, Ancylostoma ceylanicum; Hs, Homo sapiens; Bt, Bos taurus; Pc, Pseudosciaena crocea; Mm, Mus musculus; Sm, Schistosoma mansoni; Pv, Plasmodium vivax; Sc, S. cerevisiae; Hp, Helicobacter pylori; Mt, Mycobacterium tuberculosis; Se, Salmonella enterica. b, 3D alignment of cation-independent 2-Cys Prx showing the highly conserved water that links the Asp/Ser cluster at the A-type interface. Note the high conservation at positions 108 and 109 in contrast with the higher variability at position 112 (facultative role in cation or water coordination) and position 76 (the main chain involved in cation/water binding). PDB accession codes are in parentheses.