Enterococcus faecalis homoserine kinase (HSK) (HSK)

Enterococcus faecalis homoserine kinase (HSK), also known as ThrB, is an essential enzyme that catalyzes the ATP-dependent phosphorylation of L-homoserine to L-homoserine phosphate (UniProt: P0C0G7). This reaction represents the first committed step in the biosynthesis of threonine and is a vital component of the aspartate metabolic pathway, which also produces methionine and isoleucine (PubMed: 21663314). Because this biosynthetic pathway is present in bacteria, fungi, and plants but entirely absent in mammals, HSK is a highly attractive target for the development of novel antimicrobial agents with high selectivity (PubMed: 25650904). Enterococcus faecalis is a significant human pathogen responsible for various healthcare-associated infections, including endocarditis and urinary tract infections, and the emergence of multi-drug resistant strains like vancomycin-resistant Enterococcus (VRE) necessitates the exploration of such alternative targets (PubMed: 16150111). Inhibition of HSK leads to the depletion of essential amino acids, resulting in the cessation of bacterial growth and protein synthesis. Although no HSK inhibitors are currently in clinical use, research into substrate analogs and small-molecule inhibitors continues to demonstrate potential for treating resistant enterococcal infections (PubMed: 28434745).

Other names

Homoserine kinaseThrBATP:L-homoserine O-phosphotransferase

Inhibition of the phosphorylation of L-homoserine to L-homoserine phosphate, disrupting the biosynthesis of essential amino acids (threonine, isoleucine, and methionine) and leading to bacterial growth inhibition.