Physiological magnesium-dependent enzymes and proteins (Mg-dependent enzymes) (Mg-dependent enzymes)

Physiological magnesium-dependent enzymes and proteins represent a diverse group of biological molecules that require divalent magnesium ions (Mg2+) for catalytic activity or structural stability. Magnesium serves as a mandatory cofactor for more than 300 to 600 enzymatic reactions, most notably those involving the utilization or synthesis of ATP, where Mg2+ coordinates with phosphate groups to facilitate phosphoryl transfer [1][2]. These proteins are integral to fundamental cellular processes, including DNA and RNA polymerization, protein synthesis, and the maintenance of genomic stability [3]. Clinically, the dysfunction or deficiency of these magnesium-dependent systems is associated with a wide range of pathologies, such as cardiovascular disease, type 2 diabetes, and various neuromuscular disorders [1][4]. Pharmacological management often involves direct magnesium supplementation to support these enzymatic functions or the administration of drugs that modulate magnesium-dependent transporters and channels [2][5]. Because magnesium is ubiquitous in metabolic pathways, its homeostasis is a critical factor in drug safety and therapeutic efficacy across multiple medical disciplines [1]. Sources: [1] NIH ODS; [2] StatPearls; [3] Physiol Rev 2015; [4] Int J Endocrinol 2018; [5] Clin Kidney J 2012.

Other names

Magnesium-dependent proteinsMg2+-dependent enzymesMagnesiotropic proteinsMagnesium-binding proteins

Magnesium functions as a co-substrate or allosteric activator for enzymes, primarily by binding to the oxygen atoms of phosphate groups in ATP and other nucleotides to stabilize their structure and facilitate nucleophilic attack [1][2]. It also acts as a structural component in ribosomes and nucleic acids, ensuring proper folding and function [3]. Drugs targeting these systems typically act by replenishing magnesium levels (supplementation), inhibiting specific magnesium-dependent enzymes (e.g., certain kinases), or modulating the transport proteins that regulate magnesium flux across cell membranes [4][5].