Fig. 1: ThyA- and ThyX-dependent folate cycles.
From: Bacterial origins of thymidylate metabolism in Asgard archaea and Eukarya
a ThyA catalyzes the methylation of dUMP to dTMP, leading to the formation of H2folate that is subsequently reduced by FolA (left panel). The flavoenzyme ThyX uses methylene from CH2H4folate and acquires the reducing hydride from NADPH. CH2H4folate functions only as carbon source, resulting in H4folate at the end of the catalytic cycle (right panel). Serine hydroxymethyltransferase GlyA is universally present. b Psyn thyX is located between the nucleotides 765,745 and 764,847 on the genome of Psyn (NZ_CP042905, 4 427 796 bp). The Psyn thyX gene is surrounded by the nif3 and DUF2095 genes. For details, see text. Structure-based sequence alignment of Psyn ThyX with Thermotoga maritima ThyX (corresponding to PDB structure 5CHP) is also shown. Functionally important residues are indicated above the alignment. Asterisks refer to folate binding, stars to nucleotide-binding and filled circles to flavin binding residues. c Structural model for the Psyn ThyX homotetramer (left panel) using PDB structures 1O26, 3N0B and 6J61 as templates. Superposition of the model with PDB structure 4GT9 allowed the addition of FAD (cyan), dUMP (yellow), and folate (green) molecules (middle panel) to the structural model. The substrate and co-factor configuration is highlighted in the right panel.
