Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Sep 1;1871(5):140931.
doi: 10.1016/j.bbapap.2023.140931. Epub 2023 Jun 21.

The Fe and Zn cofactor dilemma

Jiahua Chen  1 , Logan A Calderone  1 , Luying Pan  1 , Trent Quist  1 , Maria-Eirini Pandelia  2
Affiliations
Review

The Fe and Zn cofactor dilemma

Jiahua Chen et al. Biochim Biophys Acta Proteins Proteom. .

Abstract

Fe and Zn ions are essential enzymatic cofactors across all domains of life. Fe is an electron donor/acceptor in redox enzymes, while Zn is typically a structural element or catalytic component in hydrolases. Interestingly, the presence of Zn in oxidoreductases and Fe in hydrolases challenge this apparent functional dichotomy. In hydrolases, Fe either substitutes for Zn or specifically catalyzes certain reactions. On the other hand, Zn can replace divalent Fe and substitute for more complex Fe assemblies, known as Fe-S clusters. Although many zinc-binding proteins interchangeably harbor Zn and Fe-S clusters, these cofactors are only sometimes functional proxies.

Keywords: Fe-S clusters; Hydrolases; Viral proteins; Zinc-finger proteins.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1.
Fig. 1.
Active site structures of metallophosphatases that utilize Fe and/or Zn ions for hydrolysis. The metal ions are represented with spheres, Fe (orange), Zn (blue-gray), Mn (purple), and Mg (green).
Fig. 2.
Fig. 2.
Active site structures of metallohydrolases that can utilize Fe and/or Zn ions for hydrolysis. The metal ions are represented with spheres, Fe (orange), Zn (blue-gray), Mg (green), and Co (pink).
Fig. 3.
Fig. 3.
Structures and structural models of proteins annotated to be Zn-dependent that have been found to coordinate Fe-Scofactors. (Left) Zn and Fe-S cluster coordination by the classical CCCH ZF-binding motif. (Middle) Zn and Fe-S cluster coordination by a CDCC binding motif occurring in proteins related to Fe-S cluster biogenesis. (Right) Structural model, Mössbauer spectra, and competitive Fe/Zn binding by the HBV protein HBx. HBx contains nine conserved cysteines and one histidine as likely cofactor ligands. HBx co-purifies with Fe and Zn ions under different metal supplementation conditions, but the role of these cofactors in HBx is still unknown. The right panel of the figure has been adapted from reference [17].
See this image and copyright information in PMC

References

    1. Andreini C, Bertini I, Cavallaro G, Holliday GL, Thornton JM, Metal ions in biological catalysis: from enzyme databases to general principles, J. Biol. Inorg. Chem. 13 (2008) 1205–1218. - PubMed
    1. Holm RH, Kennepohl P, Solomon EI, Structural and functional aspects of metal sites in biology, Chem. Rev. 96 (7) (1996) 2239–2314. - PubMed
    1. McCall KA, Huang C-C, Fierke CA, Function and mechanism of zinc Metalloenzymes, J. Nutr. 130 (5) (2000) 1437S–1446S. - PubMed
    1. Weston J, Mode of action of bi- and Trinuclear zinc hydrolases and their synthetic analogues, Chem Revs 105 (6) (2005) 2151–2174. - PubMed
    1. Pierre J, Fontecave M, Iron and activated oxygen species in biology: the basic chemistry, Biometals 12 (3) (1999) 195. - PubMed

Publication types

LinkOut - more resources