Metalloproteins and their metals

JBC thematic minireview series on metals in biology continues

Metal ions are essential for the function of more than one-third of all proteins. Many enzyme-aided processes, such as nutrient absorption and excretion, require certain metal ions at optimum concentrations both inside and outside of the cells. The Journal of Biological Chemistry recently published the sixth installment of an ongoing series about the role of metals in biochemistry and human health. This year’s “Metals in Biology” series, coordinated by JBC Associate Editor F. Peter Guengerich of Vanderbilt University, features five review articles that describe metal homeostasis in terms of enzyme selectivity and affinity for certain metals and the consequences of the wrong metal attaching to an enzyme during a reaction known as mismetallation.

In the first minireview, a group of authors led by Nigel Robinson from Durham University in the U.K. discusses enzymes’ metallation selectivity processes and the implications of metal deficiency. Under deficient conditions, enzymes compete for metal ions in buffered metal pools inside the cells. As an example, the authors discuss the competition between Zn2+ and Mg2+ and Fe2+and Mn2+ in the context of metal-delivery systems in metal homeostasis.

In the second minireview, JoAnne Stubbe from the Massachusetts Institute of Technology and co-authors describe the competition between Fe2+ and Mn2+ for ribonucleotide reductase. They discuss how organisms use either one or both of these metals in this enzyme and how perturbed environmental and genetic conditions cause mismetallation.

In the third minireview, John Helmann from Cornell University reviews the key factors regulating Fe2+ and Mn2+ homeostasis in the model organism Bacillus subtilis. The Gram-positive bacterium provides a model for the regulation of Fe2+ and Mn2+ homeostasis that involves three regulatory proteins, Fur, MntR and PerR, to sense the intracellular levels of Fe2+ and Mn2+ and the ratio between them.

The fourth minireview, by James Imlay from University of Illinois at Urbana–Champaign, discusses how oxidative stress causes mismetallation. Using E. coli as an example, he explains how oxidation of Fe2+ by partially reduced O2 species perturbs the competition between Fe2+, Zn2+ and Mn2+.

The fifth minireview, by Crysten Blaby-Haas at the University of California, Los Angeles, delves into the role of metal transporters in storage organelles for loading and unloading the metal. Along with animal systems, yeast- and plant-based models have contributed to our understanding of vacuoles and related organelles as mediators of metal homeostasis.

Umesh D. WankhadeUmesh Wankhade ( is a postdoctoral fellow at National Institute of Health’s Diabetes, Endocrinology and Obesity branch.

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We hope you enjoy this excerpt from a Journal of Biological Chemistry Paper of the Week author profile as much as we did.

Although I have received previous awards for various poster and oral presentations at CWRU, I take particular pride in winning the department’s legendary Stall-Pewis Award for excellence in the field of blooper biochemistry. My award-winning miscues in the laboratory have, therefore, become part of a legacy of bloopers shared by such late legends as professors Harland Wood and Richard Hanson. (Corresponding author Michael Weiss) and I dedicate this present recognition to their memory.”

- Joseph Racca, a graduate student at Case Western Reserve University School of Medicine and the first author of the JBC Paper of the Week titled "Structure-function relationships in human testis-determining factor SRY: An aromatic buttress underlies the specific DNA-bending surface of an HMG box."