The biochemical and X-ray crystallography-based characterization of human dihydroorotate dehydrogenase (DHODH) in complex with a potent antiproliferative agent is presented. The peculiar conformation of a protein loop involved in the gating mechanism at the cofactor-binding site reveals a new binding modality of the tested compound that will contribute to a reappraisal of the inhibition of human DHODH.

This paper reports the structure of Δ¹-pyrroline-2-carboxylate reductase from the archaeon T. litoralis, a key enzyme in the second step of trans-4-hydroxy-L-proline metabolism that is conserved in archaea, bacteria and humans.