PydAc is a variant of PydA present in anaerobic bacteria
(A) Comparison of the crystal structure of Sus scrofa dihydropyrimidine dehydrogenase (PDB: 1GTE) with a homology model of Clostridium chromiireducens PydAc [7]. For the S. scrofa enzyme, the homodimer is shown, with the Fdx1 (red), FAD/NADPH (blue) and FMN (green) domains of subunit 1, and the Fdx2 (yellow) domain of subunit 2. Cofactors and a substrate analog are rendered in spheres. The substrate analog 5-ioduracil (purple) is located in the FMN domain. The pathway for electron transfer from the FAD to the FMN site is indicated. For the C. chromiireducens enzyme, the same color scheme and rendering is used, showing the lack of the FAD/NADPH domain. The proposed pathway for electron transfer from the putative electron source reduced Fdx to the FMN site is indicated. (B) Comparison of the domain structures of PydA variants, including the previously characterized NADP-dependent dihydropyrimidine dehydrogenase from S. scrofa (SsPydA), NAD-dependent dihydropyrimidine dehydrogenase from Escherichia coli (EcPreAT), and two putative Clostridial ferredoxin-dependent dihydropyrimidine dehydrogenases from C. chromiireducens and C. pasteurianum (CcPydAc and CpPydAc). (C) Pyd gene clusters in bacteria. PydA, dihydropyrimidine dehydrogenase; PydB, dihydropyrimidinase; PydC, ureidopropionase; PydD, β-alanine aminotransferase; PydE, malonic semialdehyde reductase; MSDH, malonic semialdehyde dehydrogenase; PydA1, dihydropyrimidine dehydrogenase Fdx1 and FAD / NADPH domains; PydA2, dihydropyrimidine dehydrogenase FMN and Fdx2 domains; PydAc, Clostridial dihydropyrimidine dehydrogenase homolog.