Bacterial enolase (ENO)

Bacterial enolase (EC 4.2.1.11) is a highly conserved metalloenzyme that catalyzes the reversible dehydration of 2-phosphoglycerate to phosphoenolpyruvate during glycolysis (UniProtKB - P0A6P0). Beyond its central metabolic role, it is a well-characterized moonlighting protein that localizes to the cell surface in various pathogens, such as Streptococcus pneumoniae and Mycobacterium tuberculosis (PMID: 24508251). On the surface, it acts as a receptor for host plasminogen, facilitating bacterial invasion and dissemination by promoting the degradation of the extracellular matrix (PMID: 19103600). Because it is essential for the growth of many bacteria and contributes directly to pathogenesis, it is considered a promising target for novel antibacterial agents (PMID: 29933149). Small molecule inhibitors like phosphonoacetohydroxamate (PhAH) and the natural product SF2312 target the enzyme's active site by mimicking the transition state (PMID: 27531905). However, the high structural similarity between bacterial enolases and human isoforms (ENO1, ENO2, and ENO3) poses a significant challenge for achieving therapeutic selectivity and avoiding host toxicity (PMID: 31630471).

Other names

2-phospho-D-glycerate hydro-lyasePhosphopyruvate hydrataseEnolase 1Eno

Competitive inhibition of the catalytic site by transition-state analogs or substrate mimics, preventing the conversion of 2-phosphoglycerate to phosphoenolpyruvate and disrupting bacterial energy metabolism (PMID: 27531905).