Bacterial sensors define intracellular free energies for correct enzyme metalation

Osman, Deenah; Martini, Maria Alessandra; Foster, Andrew W.; Chen, Junjun; Scott, Andrew J.P.; Morton, Richard J.; Steed, Jonathan W.; Lurie-Luke, Elena; Huggins, Thomas G.; Lawrence, Andrew D.; Deery, Evelyne; Warren, Martin J.; Chivers, Peter T.; Robinson, Nigel J.

Abstract

There is a challenge for metalloenzymes to acquire their correct metals because some inorganic elements form more stable complexes with proteins than do others. These preferences can be overcome provided some metals are more available than others. However, while the total amount of cellular metal can be readily measured, the available levels of each metal have been more difficult to define. Metal-sensing transcriptional regulators are tuned to the intracellular availabilities of their cognate ions. Here we have determined the standard free energy for metal complex formation to which each sensor, in a set of bacterial metal sensors, is attuned: the less competitive the metal, the less favorable the free energy and hence the greater availability to which the cognate allosteric mechanism is tuned. Comparing these free energies with values derived from the metal affinities of a metalloprotein reveals the mechanism of correct metalation exemplified here by a cobalt chelatase for vitamin B12.

Citation

Osman, D., Martini, M. A., Foster, A. W., Chen, J., Scott, A. J., Morton, R. J., …Robinson, N. J. (2019). Bacterial sensors define intracellular free energies for correct enzyme metalation. Nature Chemical Biology, 15(3), 241-249. https://doi.org/10.1038/s41589-018-0211-4

• Journal Article Type: Article
• Acceptance Date: Dec 4, 2018
• Online Publication Date: Jan 28, 2019
• Publication Date: Mar 31, 2019
• Deposit Date: Nov 21, 2018
• Publicly Available Date: Jul 28, 2019
• Journal: Nature Chemical Biology
• Print ISSN: 1552-4450
• Electronic ISSN: 1552-4469
• Publisher: Nature Research
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Issue: 3
• Pages: 241-249
• DOI: https://doi.org/10.1038/s41589-018-0211-4
• Public URL: https://durham-repository.worktribe.com/output/1313312
• Publisher URL: https://rdcu.be/biPEi