Uroporphyrinogen III decarboxylase

1JPH, 1JPI, 1JPK, 1R3Q, 1R3R, 1R3S, 1R3T, 1R3V, 1R3W, 1R3Y, 1URO, 2Q6Z, 2Q71, 3GVQ, 3GVR, 3GVV, 3GVW, 3GW0, 3GW3738922275ENSG00000126088ENSMUSG00000028684P06132P70697NM_000374NM_009478NP_000365NP_033504Uroporphyrinogen III decarboxylase (uroporphyrinogen decarboxylase, or UROD) is an enzyme (EC 4.1.1.37) that in humans is encoded by the UROD gene.1jph: Ile260Thr mutant of Human UroD, human uroporphyrinogen III decarboxylase1jpi: Phe232Leu mutant of human UROD, human uroporphyrinogen III decarboxylase1jpk: Gly156Asp mutant of Human UroD, human uroporphyrinogen III decarboxylase1r3q: Uroporphyrinogen Decarboxylase in complex with coproporphyrinogen-I1r3r: Uroporphyrinogen Decarboxylase with mutation D86N1r3s: Uroporphyrinogen Decarboxylase single mutant D86G in complex with coproporphyrinogen-I1r3t: Uroporphyrinogen Decarboxylase single mutant D86G in complex with coproporphyrinogen-III1r3v: Uroporphyrinogen Decarboxylase single mutant D86E in complex with coproporphyrinogen-I1r3w: Uroporphyrinogen Decarboxylase Y164F mutant in complex with coproporphyrinogen-III1r3y: Uroporphyrinogen Decarboxylase in complex with coproporphyrinogen-III1uro: UROPORPHYRINOGEN DECARBOXYLASE Uroporphyrinogen III decarboxylase (uroporphyrinogen decarboxylase, or UROD) is an enzyme (EC 4.1.1.37) that in humans is encoded by the UROD gene. Uroporphyrinogen III decarboxylase is a homodimeric enzyme (PDB: 1URO​) that catalyzes the fifth step in heme biosynthesis, which corresponds to the elimination of carboxyl groups from the four acetate side chains of uroporphyrinogen III to yield coproporphyrinogen III: Mutations and deficiency in this enzyme are known to cause familial porphyria cutanea tarda and hepatoerythropoietic porphyria. At low substrate concentrations, the reaction is believed to follow an ordered route, with the sequential removal of CO2 from the D, A, B, and C rings, whereas at higher substrate/enzyme levels a random route seems to be operative. The enzyme functions as a dimer in solution, and both the enzymes from human and tobacco have been crystallized and solved at good resolutions. UroD is regarded as an unusual decarboxylase, since it performs decarboxylations without the intervention of any cofactors, unlike the vast majority of decarboxylases. Its mechanism has recently been proposed to proceed through substrate protonation by an arginine residue. A 2008 report demonstrated that the uncatalyzed rate for UroD's reaction is 10−19 s−1, so at pH 10 the rate acceleration of UroD relative to the uncatalyzed rate, i.e. catalytic proficiency, is the largest for any enzyme known, 6 x 1024 M−1.