InterPro: IPR000257 Uroporphyrinogen decarboxylase (URO-D)

Uroporphyrinogen decarboxylase (URO-D), the fifth enzyme of the haem biosynthetic pathway, catalyses the sequential decarboxylation of the four acetyl side chains of uroporphyrinogen to yield coproporphyrinogen [1]. URO-D deficiency is responsible for the human genetic diseases familial porphyria cutanea tarda (fPCT) and hepatoerythropoietic porphyria (HEP). The sequence of URO-D has been well conserved throughout evolution. The best conserved region is located in the N-terminal section; it contains a perfectly conserved hexapeptide. There are two arginine residues in this hexapeptide which could be involved in the binding, via salt bridges, to the carboxyl groups of the propionate side chains of the substrate.

The crystal structure of human uroporphyrinogen decarboxylase shows it as comprised of a single domain containing a (beta/alpha)8-barrel with a deep active site cleft formed by loops at the C-terminal ends of the barrel strands. URO-D is a dimer in solution. Dimerisation juxtaposes the active site clefts of the monomers, suggesting a functionally important interaction between the catalytic centres [2].