Coproheme Decarboxylase

Abstract

Coproheme decarboxylases are essential enzymes within prokaryotic heme biosynthesis. These pentameric enzymes catalyze the ultimate reaction of the so‐called coproporphyrin‐dependent pathway, yielding the final product heme b by oxidative decarboxylation of two propionate groups of the substrate coproheme. The reaction occurs in a stepwise manner and transiently produces a three‐propionate intermediate during catalysis. In coproheme decarboxylases, the iron‐containing porphyrin substrate is the essential redox‐active molecule, which is required for the decarboxylation of the propionate groups and formation of the heme b vinyls. The reaction is initiated by an oxidant, most likely hydrogen peroxide, to lift the ferric iron of coproheme to the two‐electron‐deficient coproheme‐Compound I species. A catalytic tyrosine, in close proximity to the propionate to be cleaved, delivers an electron to form a neutral tyrosyl radical, which further attacks the β‐carbon of the propionate group and triggers the decarboxylation reaction, yielding a carbon dioxide molecule and a remaining vinyl group on the porphyrin. Structurally, coproheme decarboxylases are described by five subunits, which are arranged in a ring‐like manner to form the homopentameric enzyme. One subunit is built of two ferredoxin‐like folds, which are connected by a flexible linker. The C‐terminal domain is the catalytically relevant one, which is able to bind coproheme.

Reorienting Mechanism of Harderoheme in Coproheme Decarboxylase—A Computational Study

“…There is more than one pathway for heme b biosynthesis, including the protoporphyrin-dependent pathway (PPD) in Gram-negative bacteria and the coproporphyrin-dependent pathway (CPD) in Gram-positive bacteria [ 8 , 9 ]. Both the PPD and CPD pathways share a common process in the final stage to decarboxylate coproheme into heme b by employing H 2 O 2 as the oxidant, in which coproheme is decarboxylated on two propionates at position 2 and position 4 sequentially by coproheme decarboxylase (ChdC) [ 10 , 11 , 12 , 13 , 14 ].…”