W0064

Crystal Structure of Ferrochelatase - the Terminal Enzyme in Heme Biosynthesis. S. Al-Karadaghi¹, M. Hansson², S. Nikonov¹, L. Hederstedt³, D. Lecerof¹ & A. Hansson², ¹Departments of Molecular Biophysics, ²Biochemistry & ³Microbiology, Lund University, Lund, Sweden

Metallation of closed ring tetrapyrroles like heme, chlorophyll and vitamin B₁₂ is catalysed by specific enzymes, chelatases. In heme biosynthesis the terminal step, metallation of protoporphyrin IX, is catalysed by ferrochelatase. No three-dimentional structure of a tetrapyrrole metallation enzyme has been known until now and the reaction mechanism at the molecular level is poorly understood.

The three-dimensional structure of ferrochelatase from Bacillus subtilis has been determined at 1.9 Å by the method of multiple isomorphus replacement. The structure consists of two similarly folded domains each with a four-stranded parallel (-sheet flanked by ( helices.

The overall three-dimentional structure of the core region of the protein seems to be conserved among different species. We have identified the porphyrin binding cleft and shown that the conserved histidine 183 is involved in metal binding. A model for porphyrin binding is proposed.