Histidinol-phosphate aminotransferase (HspAT)

Histidinol-phosphate aminotransferase (HspAT), also known as HisC, is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the seventh step in the de novo biosynthesis of L-histidine (UniProt, Wikipedia). It facilitates the reversible transamination of L-histidinol phosphate and 2-oxoglutarate to produce imidazole acetol phosphate and L-glutamate (KEGG, PubMed). This enzyme is widely distributed among bacteria, fungi, and plants but is notably absent in humans, who must obtain histidine through their diet (PMC, Wikipedia). This absence makes HspAT an attractive target for the development of selective antimicrobial, antifungal, and herbicidal agents with minimal host toxicity (PMC, PubMed). In the context of infectious diseases, HspAT has been identified as a high-confidence drug target in Mycobacterium tuberculosis, where it is essential for survival and contributes to virulence by modulating host immune responses (UniProt, PMC). Specifically, the M. tuberculosis ortholog Rv2231c has been shown to interact with host TLR4 receptors, dampening the innate defense mechanisms of macrophages (PMC). Although no clinical drugs currently target this enzyme, experimental inhibitors such as 2-(N-morpholino)ethanesulfonic acid (MES) and various metal ions have been identified in research settings (UniProt, PubMed). Ongoing drug discovery efforts utilize structural biology and computational docking to identify potent small-molecule inhibitors that could serve as novel treatments for tuberculosis and other resistant infections (PubMed).

Other names

Histidinol-phosphate transaminaseImidazolylacetolphosphate transaminaseGlutamic-imidazoleacetol phosphate transaminaseImidazole acetol-phosphate transaminaseL-histidinol phosphate aminotransferaseHisCHIS5Rv2231c

Inhibition of L-histidine biosynthesis and pathogen virulence