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Journal of Heavy Metal Research
Quarterly Publication

The Pivotal Role of Heavy Metals in Protein Structure and Function: A Brief Review

https://doi.org/10.22034/jhmr.2026.562858.1010
Volume 1, Issue 2 - Serial Number 2
Spring 2026
Pages 20-29
Journal of Heavy Metal Research

Document Type : Review

Authors

Raja Khawarat 1
Ayesha Noor Qureshi 2

1 Institute of Molecular Biology and Biotechnology, University of Lahore, Lahore, Pakistan

2 Centre for Genomics and Bioinformatics, University of Karachi, Karachi, Pakistan

Abstract
Metal ions are integral to biological chemistry, underpinning structural organization, catalytic reactivity, and regulatory control in living systems. Current estimates indicate that roughly one-third of all proteins require a bound metal cofactor to achieve functional competence. This review examines the roles of selected first-row transition metals, nickel (Ni), chromium (Cr), zinc (Zn), copper (Cu), manganese (Mn), and cobalt (Co), in protein structure and function, emphasizing the mechanistic principles that govern their biological activity. We analyze how metal coordination shapes protein folding landscapes, stabilizes native conformations, and enables small structural domains such as zinc fingers to attain functional architecture. In contrast, we discuss how aberrant metal binding to unfolded or non-native states can disrupt folding pathways, promote aggregation, and contribute to proteotoxic stress. The catalytic versatility of these metals is explored in the context of metalloenzymes, where redox cycling and Lewis acid chemistry facilitate reactions ranging from energy metabolism to antioxidant defense. Additionally, we highlight the role of metal-responsive transcription factors that couple intracellular metal availability to gene expression, thereby maintaining homeostatic balance. Finally, we examine the pathological consequences of metal dyshomeostasis, including carcinogenesis, neurodegeneration, and cardiovascular toxicity. Together, these perspectives underscore the delicate equilibrium between essential metal utilization and metal-induced toxicity that defines metal–protein interactions in health and disease.

Keywords

Metalloprotein
Protein Folding
Metal Homeostasis
Metalloenzyme
Transcription Factor
Nickel
Metal Toxicity
Subjects
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  • Receive Date 29 November 2025
  • Revise Date 26 February 2026
  • Accept Date 11 May 2026
  • Publish Date 12 May 2026

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