The manganese/iron-carboxylate proteins: what is what, where are they, and what can the sequences tell us?

Original Paper

Abstract

The manganese/iron-carboxylate proteins make up a recently discovered group of proteins that contain a heterodinuclear Mn/Fe redox cofactor. The chemical potential of the heterodinuclear metal site is just starting to be characterized, but available data suggest that it may have capabilities for similarly versatile chemistry as the extensively studied diiron-carboxylate cofactor. The presently identified members of the manganese/iron-carboxylate proteins are all sequence homologues of the radical-generating R2 subunit of class I ribonucleotide reductase, canonically a diiron protein. They are also commonly misannotated as such in databases. In spite of the sequence similarity, the manganese/iron-carboxylate proteins form at least two functionally distinct groups, radical-generating ribonucleotide reductase subunits and ligand-binding Mn/Fe proteins. Here, the presently available sequences for the manganese/iron-carboxylate proteins are gathered, grouped, and analyzed. The analysis provides sequence determinants that allow group identification of new sequences on the single-protein level. Key differences between the groups are mapped on the known representative structures, providing clues to the structural prerequisites for metal specificity, cofactor formation, and difference in function. The organisms that encode manganese/iron-carboxylate proteins are briefly discussed; their environmental preference suggests that the Mn/Fe heterodinuclear cofactor is preferred by extremophiles and pathogens with a particularly high relative presence in Archaea.

Keywords

Heterodinuclear Metal specificity Redox tuning Oxygenase Reductase 

Notes

Acknowledgments

Britt-Marie Sjöberg is gratefully acknowledged for discussions and comments on the manuscript. This work was supported by grants from the Swedish Research Council, the Swedish Foundation for Strategic Research, and the Knut and Alice Wallenberg foundation.

Supplementary material

775_2009_606_MOESM1_ESM.pdf (543 kb)
Supplementary Figures (PDF 543 kb)

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Copyright information

© SBIC 2009

Authors and Affiliations

  1. 1.Arrhenius Laboratories for Natural Sciences C4, Department of Biochemistry and Biophysics, Stockolm Center for Biomembrane ResearchStockholm UniversityStockholmSweden

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