Homoserine kinase (HSK)

Homoserine kinase (HSK) is a key enzyme in the aspartate-derived amino acid biosynthetic pathway, catalyzing the ATP-dependent phosphorylation of L-homoserine to form L-homoserine phosphate (UniProt: P00891). This reaction is an essential step for the synthesis of threonine, isoleucine, and methionine in bacteria, fungi, and plants (PubMed: 11722154). Because this metabolic pathway and the HSK enzyme itself are entirely absent in humans and other mammals, it represents a highly selective and attractive target for the development of novel antibacterial and antifungal therapeutics (PubMed: 25613611). Inhibition of HSK leads to a deficiency in essential amino acids, effectively halting protein synthesis and microbial proliferation. Current drug discovery efforts focus on identifying potent small-molecule inhibitors that can overcome antibiotic resistance by targeting this unique microbial vulnerability (PubMed: 15659344).

Other names

L-homoserine kinaseATP:L-homoserine O-phosphotransferasethrB

Inhibition of homoserine kinase disrupts the aspartate-derived amino acid biosynthetic pathway, leading to the depletion of essential amino acids such as threonine and isoleucine, which results in the inhibition of microbial protein synthesis and growth (PubMed: 15659344).