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The coproporphyrin ferrochelatase of Staphylococcus aureus: mechanistic insights into a regulatory iron binding site

Hobbs, Charlie, Reid, J.D., Shepherd, Mark (2017) The coproporphyrin ferrochelatase of Staphylococcus aureus: mechanistic insights into a regulatory iron binding site. Biochemical Journal, 474 (20). pp. 3513-3522. ISSN 0264-6021. (doi:10.1042/BCJ20170362) (KAR id:62979)

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http://dx.doi.org/10.1042/BCJ20170362

Abstract

The majority of characterised ferrochelatase enzymes catalyse the final step of classical haem synthesis, inserting ferrous iron into protoporphyrin IX. However, for the recently-discovered coproporphyrin-dependent pathway, ferrochelatase catalyses the penultimate reaction where ferrous iron is inserted into coproporphyrin III. Ferrochelatase enzymes from the bacterial phyla Firmicutes and Actinobacteria have previously been shown to insert iron into coproporphyrin, and those from Bacillus subtilis and Staphylococcus aureus are known to be inhibited by elevated iron concentrations. The work herein reports a Km (coproporphyrin III) for S. aureus ferrochelatase of 1.5 µM and it is shown that elevating the iron concentration increases the Km for coproporphyrin III, providing a potential explanation for the observed iron-mediated substrate inhibition. Together, structural modelling, site-directed mutagenesis, and kinetic analyses confirm residue Glu271 as being essential for the binding of iron to the inhibitory regulatory site on S. aureus ferrochelatase, providing a molecular explanation for the observed substrate inhibition patterns. This work therefore has implications for how haem biosynthesis in S. aureus is regulated by iron availability.

Item Type: Article
DOI/Identification number: 10.1042/BCJ20170362
Additional information: will be Gold OA once published - pls. change license/embargo
Uncontrolled keywords: Coproporphyrinogen, ferrochelatase, haem biosynthesis
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Mark Shepherd
Date Deposited: 07 Sep 2017 12:28 UTC
Last Modified: 23 Jan 2020 04:13 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/62979 (The current URI for this page, for reference purposes)
Shepherd, Mark: https://orcid.org/0000-0002-7472-2300
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