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An evolutionary path to altered cofactor specificity in a metalloenzyme

Lookup NU author(s): Dr Anna Barwinska-SendraORCiD, Dr Kacper Sendra, Dr Arnaud Basle, Eilidh Mackenzie, Dr Emma Tarrant, Dr Cedric Bicep, Dr Kevin WaldronORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2020, The Author(s).Almost half of all enzymes utilize a metal cofactor. However, the features that dictate the metal utilized by metalloenzymes are poorly understood, limiting our ability to manipulate these enzymes for industrial and health-associated applications. The ubiquitous iron/manganese superoxide dismutase (SOD) family exemplifies this deficit, as the specific metal used by any family member cannot be predicted. Biochemical, structural and paramagnetic analysis of two evolutionarily related SODs with different metal specificity produced by the pathogenic bacterium Staphylococcus aureus identifies two positions that control metal specificity. These residues make no direct contacts with the metal-coordinating ligands but control the metal’s redox properties, demonstrating that subtle architectural changes can dramatically alter metal utilization. Introducing these mutations into S. aureus alters the ability of the bacterium to resist superoxide stress when metal starved by the host, revealing that small changes in metal-dependent activity can drive the evolution of metalloenzymes with new cofactor specificity.

Publication metadata

Author(s): Barwinska-Sendra A, Garcia YM, Sendra KM, Baslé A, Mackenzie ES, Tarrant E, Card P, Tabares LC, Bicep C, Un S, Kehl-Fie TE, Waldron KJ

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2020

Volume: 11

Issue: 1

Online publication date: 01/06/2020

Acceptance date: 29/04/2020

Date deposited: 20/01/2021

ISSN (electronic): 2041-1723

Publisher: Nature Research


DOI: 10.1038/s41467-020-16478-0

PubMed id: 32483131


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Funder referenceFunder name
Wellcome Trust