Phosphopyruvate hydratase (Enolase) (ENO)

Phosphopyruvate hydratase, commonly known as enolase, is a vital glycolytic enzyme that catalyzes the reversible conversion of 2-phosphoglycerate to phosphoenolpyruvate [1]. In humans, it exists as three distinct isoforms: alpha-enolase (ENO1), beta-enolase (ENO3), and gamma-enolase (ENO2), which are expressed in a tissue-specific manner [2]. Beyond its central role in energy metabolism, enolase is recognized as a moonlighting protein that can localize to the cell surface, where it acts as a receptor for plasminogen, facilitating extracellular matrix degradation and cell invasion [3]. This dual functionality makes it a target of interest in oncology, particularly through the concept of collateral lethality, where ENO2 inhibitors are used to selectively kill cancer cells that have lost the ENO1 gene through chromosomal deletions [4]. Furthermore, the gamma isoform, also known as neuron-specific enolase (NSE), is a well-established clinical biomarker for monitoring neuroendocrine tumors and assessing the severity of traumatic brain injury [5]. In addition to cancer, enolase is targeted in the development of antimicrobial agents, as many pathogens rely on surface-expressed enolase for host tissue colonization [6]. Therapeutic strategies currently include small molecule inhibitors of the active site and monoclonal antibodies targeting the surface-exposed enzyme [3]. Sources: [1] UniProt Consortium. Enolase 1 (P06733). [2] NCBI Gene. ENO1 enolase 1 [Homo sapiens]. [3] Capello, M., et al. (2011). Alpha-enolase: a promising therapeutic and diagnostic tumor target. [4] Muller, F. L., et al. (2012). Passenger deletions generate therapeutic vulnerabilities in cancer. Nature. [5] Isgrò, M. A., et al. (2015). Neuron-Specific Enolase (NSE) as a Biomarker. Advances in Cancer Research. [6] Avilán, L., et al. (2011). Enolase: a moonlighting protein as a bacterial virulence factor.

Other names

Enolase2-phospho-D-glycerate hydro-lyaseAlpha-enolase (ENO1)Beta-enolase (ENO3)Gamma-enolase (ENO2)Neuron-specific enolase (NSE)

Inhibition of the magnesium-dependent enzymatic conversion of 2-phosphoglycerate to phosphoenolpyruvate, thereby disrupting glycolytic flux and ATP production in susceptible cells [1, 4].