Ferrochelatase at the millennium: structures, mechanisms and [2Fe-2S] clusters

Ferrochelatase (E.C. 4.99.1.1, protoheme ferrolyase) catalyzes the insertio n of ferrous iron into protoporphyrin IX to form protoheme theme). In the p ast 2 years, the crystal structures of ferrochelatases from the bacterium B acillus subtilis and human have been determined. These structures along wit h years of biophysical and kinetic studies have led to a better understandi ng of the catalytic mechanism of ferrochelatase. At present, the complete D NA sequences of 45 ferrochelatases from procaryotes and eucaryotes are avai lable. These sequences along with direct protein studies reveal that ferroc helatases, while related,,vary significantly in amino acid sequence, molecu lar size, subunit composition, solubility, and the presence or absence of n itric-oxide-sensitive [2Fe-2S] cluster.