Uroporphyrinogen III decarboxylase is a homodimeric enzyme (PDB:1URO) that catalyzes the fifth step inheme biosynthesis, which corresponds to the elimination ofcarboxyl groups from the fouracetate side chains of uroporphyrinogen III to yield coproporphyrinogen III:[6]
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.
The reaction catalyzed by UroD
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 been proposed to proceed through substrate protonation by anarginine residue.[8] 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.[6]
Proposed reaction mechanism of uroporphyrinogen III decarboxylase
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