The PRODH fold. The structure of DrPRODH complexed with THFA is shown (PDB code 4H6Q). FAD is colored yellow; THFA is colored gray. The strands and helices of the (βα)8 barrel are labeled. Upper inset: Close-up view of the FAD isoalloxazine and THFA. The N5 atom of the FAD is the hydride acceptor. The C5 atom of THFA represents the hydride donor of proline. The distance between these two atoms in the structure is 3.2 Å. Lower inset: Sequence alignment of α8 residues from diverse PRODHs. At, Arabidopsis thaliana; Dr, Deinococcus radiodurans; Ec, Escherichia coli; FAD, flavin adenine dinucleotide; Gs, Geobacter sulfurreducens; Hs, Homo sapiens; PDB, Protein Data Bank; PRODH, proline dehydrogenase; Sc, Saccharomyces cerevisiae; Tc, Trypanosoma cruzi; THFA, l-tetrahydrofuroic acid. This figure and others were created with PyMOL (26). To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars