Journal article
An evolutionary path to altered cofactor specificity in a metalloenzyme
Nature communications, Vol.11(1), pp.2738-2738
06/01/2020
DOI: 10.1038/s41467-020-16478-0
PMCID: PMC7264356
PMID: 32483131
Abstract
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.
Details
- Title: Subtitle
- An evolutionary path to altered cofactor specificity in a metalloenzyme
- Creators
- Anna Barwinska-Sendra - Newcastle UniversityYuritzi M. Garcia - University of Illinois Urbana-ChampaignKacper M. Sendra - Newcastle UniversityArnaud Basle - Newcastle UniversityEilidh S. Mackenzie - Newcastle UniversityEmma Tarrant - Newcastle UniversityPatrick Card - Newcastle UniversityLeandro C. Tabares - Institut de Biologie Intégrative de la CelluleCedric Bicep - Newcastle UniversitySun Un - Institut de Biologie Intégrative de la CelluleThomas E. Kehl-Fie - University of Illinois Urbana-ChampaignKevin J. Waldron - Newcastle University
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.11(1), pp.2738-2738
- Publisher
- NATURE PORTFOLIO
- DOI
- 10.1038/s41467-020-16478-0
- PMID
- 32483131
- PMCID
- PMC7264356
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Number of pages
- 13
- Grant note
- 204877/Z/16/Z / Wellcome Trust Collaborative Award; Wellcome Trust Vallee Foundation R01 AI118880 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA BBSRC; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC) 098375/Z/12/Z / Royal Society BBSRC Ph.D. studentship; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC) ANR-10-INBS-05 / French Infrastructure for Integrated Structural Biology (FRISBI) 098375/Z/12/Z / Wellcome Trust Newcastle University's Faculty of Medical Sciences
- Language
- English
- Date published
- 06/01/2020
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984618516102771
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