Bioinorganic Chemistry

Bioinorganic chemistry explores how metal ions interact with biological molecules to underpin life’s essential processes. Metals serve as structural elements in proteins, as in Zn-finger motifs and calcium-binding domains, and as catalytic centres in metalloenzymes that catalyse redox, acid–base and group‐transfer reactions. Iron and copper modulate electron-transfer chains in respiration and photosynthesis, whereas zinc and magnesium stabilise macromolecular structures and activate hydrolytic enzymes. Transition metals such as nickel, cobalt and molybdenum appear in specialised cofactors for hydrogen evolution, methyl transfers and nitrogen fixation. Beyond catalysis, metals act as signals and sensors—iron–sulfur clusters and heme centres detect oxidative stress, while calcium and lanthanides regulate cellular responses. Imbalances in metal homeostasis are implicated in disease, and metalloprotein mechanisms guide the design of diagnostic agents, drug targets and sustainable catalysts.

Research from Nature Portfolio

Co-translocational metalation has emerged as a key principle in the assembly of secreted metalloenzymes. Studies of a widely conserved family of membrane transporters reveal that they associate with the general secretion (Sec) pathway to deliver manganese ions into nascent proteins as they emerge from the translocon. Disruption of these transporters compromises the activity of extracytoplasmic enzymes and undermines cell-envelope integrity, highlighting how metal insertion is coupled to protein export.

Insights into the evolution of metal specificity have come from an extensive survey of superoxide dismutases (SODs), enzymes that detoxify superoxide radicals using either iron or manganese. Phylogenetic and biochemical analyses show that a small number of conserved active-site residues shift SOD metal preference along a continuum of iron- to manganese-specificity. This metal-tuning capacity has been independently selected multiple times across diverse bacterial lineages in response to changing environmental metal availability, demonstrating evolutionary plasticity of metalloenzyme function.

Bioinorganic Chemistry publication trend

The graph below shows the total number of articles in bioinorganic chemistry across all publications each year (not limited to Nature Index journals).

Technical terms

Metalloenzyme: A protein containing a metal ion cofactor essential for catalytic activity.

Co-translocational metalation: Insertion of a metal ion into a protein’s active site concurrently with secretion through the membrane export machinery.

Dinitrosyl iron complex (DNIC): A coordination compound in which iron binds two nitric oxide ligands, serving as a physiological NO reservoir and signalling species.

Metal preference modulation: Evolutionary changes in active-site residues that fine-tune an enzyme’s specificity for one metal ion over another.

References

1. The Periodic Table’s Impact on Bioinorganic Chemistry and Biology’s Selective Use of Metal Ions.
2. TerC proteins function during protein secretion to metalate exoenzymes. Nature Communications (2023).
3. An ancient metalloenzyme evolves through metal preference modulation. Nature Ecology & Evolution (2023).
4. Mechanistic and Kinetic Insights into Cellular Uptake of Biomimetic Dinitrosyl Iron Complexes and Intracellular Delivery of NO for Activation of Cytoprotective HO‑1. JACS Au (2024).
5. Binding of a single nitric oxide molecule is sufficient to disrupt DNA binding of the nitrosative stress regulator NsrR. Chemical Science (2024).