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Metal ions in biological catalysis: from enzyme databases to general principles
Abstract
We analysed the roles and distribution of metal ions in enzymatic catalysis using available public databases and our new resource Metal-MACiE (http://www.ebi.ac.uk/thornton-srv/databases/Metal_MACiE/home.html). In Metal-MACiE, a database of metal-based reaction mechanisms, 116 entries covering 21% of the metal-dependent enzymes and 70% of the types of enzyme-catalysed chemical transformations are annotated according to metal function. We used Metal-MACiE to assess the functions performed by metals in biological catalysis and the relative frequencies of different metals in different roles, which can be related to their individual chemical properties and availability in the environment. The overall picture emerging from the overview of Metal-MACiE is that redox-inert metal ions are used in enzymes to stabilize negative charges and to activate substrates by virtue of their Lewis acid properties, whereas redox-active metal ions can be used both as Lewis acids and as redox centres. Magnesium and zinc are by far the most common ions of the first type, while calcium is relatively less used. Magnesium, however, is most often bound to phosphate groups of substrates and interacts with the enzyme only transiently, whereas the other metals are stably bound to the enzyme. The most common metal of the second type is iron, which is prevalent in the catalysis of redox reactions, followed by manganese, cobalt, molybdenum, copper and nickel. The control of the reactivity of redox-active metal ions may involve their association with organic cofactors to form stable units. This occurs sometimes for iron and nickel, and quite often for cobalt and molybdenum.
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“The interaction with metals alters the physico- chemical properties of proteins, thereby promoting catalysis of enzymatic reactions, stabilizing protein structure and/or facilitating electron transport 2,3 .”
From Nutritional immunity: the battle for nutrient metals at the host–pathogen interface (2022) · cites this paper as [2]
In the citing paper
“Zinc, iron, and manganese are the most common transition metals serving critical cofactor or structural roles in mammalian and bacterial proteins (Andreini et al., 2008).”
From The Impact of Dietary Transition Metals on Host-Bacterial Interactions (2018) · cites this paper as Andreini et al., 2008
In the citing paper
“One striking example is the critical role of metal ions, particularly iron, in the activity of many enzymes involved in the detoxification of reactive oxygen species (ROS) [54–56].”
From Aprepitant, an antiemetic agent, interferes with metal ion homeostasis of Candida auris and displays potent synergistic interactions with azole drugs (2020) · cites this paper as [56]
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Metadata
- Authors
- Andreini, C., Bertini, I., Cavallaro, G., Holliday, G. L., & Thornton, J. M.
- Affiliations
- University of Florence (IT)
- European Bioinformatics Institute (GB)
- Corresponding author
- Thornton, Janet M.
- Venue
- JBIC Journal of Biological Inorganic Chemistry
- Published
- 2008-07-05
- Volume
- 13
- Issue
- 8
- Pages
- 1205-1218
- ISSN
- 0949-8257 (ISSN-L)
- 1432-1327
- OpenAlex
- W2052498582
- Cited by
- 1,150
- References
- 72
- Citations by year
- 2026: 68 · 2025: 92 · 2024: 108 · 2023: 89 · 2022: 92 · 2021: 105 · 2020: 87 · 2019: 80 · 2018: 53 · 2017: 59 · 2016: 62 · 2015: 38 · 2014: 47 · 2013: 44 · 2012: 41
- FWCI
- 16.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- JBIC Journal of Biological Inorganic Chemistry (publishedVersion)
- PubMed (publishedVersion)
- BIROn (Birkbeck, University of London) (submittedVersion)
- Florence Research (University of Florence) (submittedVersion)
- Funders
- Wellcome Trust (062347)
- Topics
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Metalloenzymes and iron-sulfur proteins
- Keywords
- metal ions, metalloenzymes, enzyme catalysis, redox-active metal ions, Lewis acid catalysis, magnesium, zinc, calcium, iron, manganese, cobalt, molybdenum, copper, nickel, cofactors
- MeSH terms
- Enzymes, Ions, Magnesium, Manganese, Metalloproteins, Metals, Models, Chemical, Oxidation-Reduction, Oxidoreductases, Transferases, Databases, Protein, Biocatalysis
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