Phosphoglycerate kinase 1 (Candida) (PGK1)

Phosphoglycerate kinase 1 (PGK1) in Candida species is a multifunctional moonlighting protein that serves as both a central glycolytic enzyme and a critical surface-associated virulence factor (PubMed: 15608311). In the cytoplasm, it catalyzes the reversible conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate, a key step in ATP generation. However, PGK1 is also translocated to the fungal cell wall, where it functions as an adhesin that binds to human plasminogen and extracellular matrix components, facilitating host tissue colonization and invasion (Journal of Fungi, 2020). This dual role makes it a significant target for the development of antifungal therapies and vaccines, as blocking its surface activity can impair the pathogen's ability to disseminate. Because of its high immunogenicity during infection, PGK1 is frequently studied alongside other surface-associated enzymes like enolase and fructose-bisphosphate aldolase as a diagnostic biomarker for invasive candidiasis (Clinical and Vaccine Immunology, 2011). While no drugs are currently approved, experimental vaccines using recombinant PGK1 have shown promise in animal models by inducing protective immune responses. The target name provided also encompasses related virulence-associated surface proteins, which refers to other moonlighting glycolytic enzymes like Enolase 1 (Eno1) and Fructose-bisphosphate aldolase (Fba1) that share similar roles in Candida pathogenesis. A major challenge in targeting PGK1 is its high structural homology with the human ortholog, necessitating high specificity to avoid off-target toxicity.

Other names

3-phosphoglycerate kinasePGKMoonlighting PGK1Cell surface PGK1Candida albicans PGK1

Inhibition of the glycolytic pathway to disrupt fungal energy production or blocking of surface-mediated host cell adhesion and plasminogen binding to prevent tissue invasion (PubMed: 15608311).