Depts. of Molecular Biophysics and Microbiology, Lund University, Sweden.
The iron containing tetrapyrrole, heme, is essential in many cell functions as a prosthetic groups in a variety of proteins involved in respiration , oxygen transport, detoxification of oxygen by-products , drug metabolism , NO synthesis. A deficiency of an enzyme in the heme biosynthesis pathway leads to a group of diseases called porphyrias, which express themselves by accumulation of tetrapyrrole biosynthetic intermediates. Heme biosynthesis pathway comprises eight (or more) enzymes. The terminal reaction in heme synthesis involves the insertion of a ferrous ion into protoporphyrin IX to form protohem IX (heme b). This reaction is catalysed by the enzyme ferrochelatase. Ferrochelatase has a molecular weight ranging between 36-40 kDa and can be found in all cells. It is associated with the cytoplasmic membrane in prokaryotes and to the inner mitochondrial membrane in eucaryotes, with its active site facing the matrix space. Ferrochelatase from Bacillus subtilis has been cloned, purified and crystallised. The structure has been solved at 2.8 ang. resolution using the method of multiple isomorphus replacement (MIR). The protein is comprised of two alpha/beta domains with a deep hydrophobic cleft between them presumably being the protoporphyrin binding site.