Escherichia coli DNA primase allosteric magnesium-binding site (DnaG allosteric Mg site)

The Escherichia coli primase (DnaG) allosteric magnesium-binding site is a critical regulatory region within the essential bacterial enzyme responsible for synthesizing RNA primers during DNA replication (Griep and Lokey, 1995). DnaG is a DNA-dependent RNA polymerase that functions as a molecular brake to coordinate the activities of the replisome on the leading and lagging strands. The enzyme contains a conserved TOPRIM domain, which includes a cluster of acidic residues that coordinate magnesium ions (Mg2+) essential for catalytic activity (CDD:240127). Biochemical studies have shown that DnaG binds at least two magnesium ions in a cooperative manner, where an allosteric magnesium-binding site induces a conformational change necessary for the enzyme to transition into its high-affinity, catalytically active state (Griep and Lokey, 1995). This site is a target for several small-molecule inhibitors, including the natural product SCH 642305 and various polyphenols, which disrupt the enzyme's function and halt bacterial proliferation (Chu et al., 2003; MDPI Molecules, 2018). Because the structure of bacterial DnaG is distinct from the human primase complex, this allosteric site represents a promising target for the development of selective, narrow-spectrum antibiotics to combat E. coli infections.

Other names

DnaG allosteric siteTOPRIM allosteric magnesium sitePrimase allosteric pocketMagnesium-binding site of DnaG

Allosteric inhibition of RNA primer synthesis by preventing the cooperative binding of magnesium ions and the subsequent conformational activation of the DnaG enzyme.