2,3-dihydroxybenzoate—serine ligase

2,3-Dihydroxybenzoate—serine ligase is an enzyme that plays a crucial role in the biosynthesis of siderophores, specifically in the synthesis of enterobactin. Siderophores are small, high-affinity iron-chelating compounds secreted by microorganisms such as bacteria and fungi. The enzyme catalyzes the ATP-dependent ligation of serine and 2,3-dihydroxybenzoate (DHB) to form 2,3-dihydroxybenzoylserine, a key intermediate in the production of enterobactin, which is essential for iron acquisition in some bacteria.

Function

The primary function of 2,3-dihydroxybenzoate—serine ligase is to facilitate the synthesis of enterobactin from serine and 2,3-dihydroxybenzoate. This process is vital for the survival of certain bacteria in iron-scarce environments. Iron is a critical nutrient for almost all living organisms, as it plays a key role in processes such as oxygen transport, DNA synthesis, and electron transport. However, free iron is rarely available in the environment, leading microorganisms to develop strategies such as the production of siderophores to sequester and utilize this essential element.

Mechanism

The enzyme operates through an ATP-dependent mechanism, where ATP is hydrolyzed to provide the energy required for the ligation of serine and DHB. This reaction proceeds through the formation of an enzyme-bound DHB-AMP intermediate, facilitating the nucleophilic attack by serine and resulting in the formation of 2,3-dihydroxybenzoylserine.

Structure

2,3-Dihydroxybenzoate—serine ligase belongs to the family of ligases, specifically those forming carbon-oxygen bonds in aminoacyl-tRNA and related compounds. The enzyme's structure has been elucidated through X-ray crystallography, revealing a complex with ATP and 2,3-dihydroxybenzoate, which provides insight into the mechanism of action and substrate specificity.

Biological Importance

The production of siderophores like enterobactin is critical for the survival of bacteria in environments where iron is limited. By chelating iron, siderophores facilitate its uptake by bacterial cells, thus supporting essential metabolic processes. The role of 2,3-dihydroxybenzoate—serine ligase in this process underscores its importance in microbial iron acquisition and offers potential targets for the development of antimicrobial agents.

Clinical Significance

Given its role in siderophore biosynthesis, 2,3-dihydroxybenzoate—serine ligase represents a potential target for novel antibacterial strategies. Inhibiting this enzyme could disrupt iron acquisition by pathogenic bacteria, thereby limiting their growth and virulence. This approach could be particularly valuable in the fight against antibiotic-resistant bacterial strains.

See Also

• Siderophore
• Iron metabolism
• Antibiotic resistance
• Ligase