Bacterial ferrochelatase turns human:Tyr13 determines the apparent metal specificity of Bacillus subtilis ferrochelatase

Hansson, Mattias D., Karlberg, Tobias, Söderberg, Christopher A.G., Rajan, Sreekanth, Warren, Martin J. ORCID:, Al-Karadaghi, Salam, Rigby, Stephen E.J. and Hansson, Mats (2011) Bacterial ferrochelatase turns human:Tyr13 determines the apparent metal specificity of Bacillus subtilis ferrochelatase. Journal of Biological Inorganic Chemistry, 16 (2). pp. 235-242. ISSN 0949-8257

Full text not available from this repository. (Request a copy)


Ferrochelatase catalyzes the insertion of Fe2+ into protoporphyrin IX. The enzymatic product heme (protoheme IX) is a well-known cofactor in a wide range of proteins. The insertion of metal ions other than Fe2+ occurs rarely in vivo, but all ferrochelatases that have been studied can insert Zn2+ at a good rate in vitro. Co2+, but not Cu2+, is known to be a good substrate of the mammalian and Saccharomyces cerevisiae ferrochelatases. In contrast, Cu2+, but not Co2+, has been found to be a good substrate of bacterial Bacillus subtilis ferrochelatase. It is not known how ferrochelatase discriminates between different metal ion substrates. Structural analysis of B. subtilis ferrochelatase has shown that Tyr13 is an indirect ligand of Fe2+ and a direct ligand of a copper mesoporphyrin product. A structure-based comparison revealed that Tyr13 aligns with a Met residue in the S. cerevisiae and human ferrochelatases. Tyr13 was changed to Met in the B. subtilis enzyme by site-directed mutagenesis. Enzymatic measurements showed that the modified enzyme inserted Co2+ at a higher rate than the wild-type B. subtilis ferrochelatase, but it had lost the ability to use Cu2+ as a substrate. Thus, the B. subtilis Tyr13Met ferrochelatase showed the same metal specificity as that of the ferrochelatases from S. cerevisiae and human.

Item Type: Article
Additional Information: Funding Information: Acknowledgments We thank Ulf Ryde for insightful discussions. M.D.H. and C.A.G.S. acknowledge IRTG—Metal Sites in Biomolecules ( This work was supported by grants from the Royal Physiographical Society in Lund (M.D.H.), the Danish Natural Science Research Council (M.H.), the Swedish Research Council (M.H., S.A.K.), the Carlsberg Foundation (M.H.), the Crafoord Foundation (M.H., S.A.K.), and the Carl Trygger Foundation (S.A.K.).
Uncontrolled Keywords: cobalt,copper,ferrochelatase,hemh,metal specificity,biochemistry,inorganic chemistry ,/dk/atira/pure/subjectarea/asjc/1300/1303
Faculty \ School: Faculty of Science
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 20 Sep 2022 15:30
Last Modified: 24 Oct 2022 16:33
DOI: 10.1007/s00775-010-0720-4

Actions (login required)

View Item View Item