Metalloallostery and Transition Metal Signaling: Bioinorganic Copper Chemistry Beyond Active Sites

Author:

Pham Vanha N.1ORCID,Chang Christopher J.123ORCID

Affiliation:

1. Department of Chemistry University of California Berkeley CA 94720 USA

2. Department of Molecular and Cell Biology University of California Berkeley CA 94720 USA

3. Helen Wills Neuroscience Institute University of California Berkeley CA 94720 USA

Abstract

AbstractTransition metal chemistry is essential to life, where metal binding to DNA, RNA, and proteins underpins all facets of the central dogma of biology. In this context, metals in proteins are typically studied as static active site cofactors. However, the emergence of transition metal signaling, where mobile metal pools can transiently bind to biological targets beyond active sites, is expanding this conventional view of bioinorganic chemistry. This Minireview focuses on the concept of metalloallostery, using copper as a canonical example of how metals can regulate protein function by binding to remote allosteric sites (e.g., exosites). We summarize advances in and prospects for the field, including imaging dynamic transition metal signaling pools, allosteric inhibition or activation of protein targets by metal binding, and metal‐dependent signaling pathways that underlie nutrient vulnerabilities in diseases spanning obesity, fatty liver disease, cancer, and neurodegeneration.

Funder

National Institute of General Medical Sciences

National Institute of Environmental Health Sciences

National Science Foundation

Publisher

Wiley

Subject

General Medicine

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