Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (GAPDH)

Bacterial glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a highly conserved enzyme that plays a central role in the glycolytic pathway by catalyzing the conversion of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate. Beyond its primary metabolic function, bacterial GAPDH is recognized as a moonlighting protein that localizes to the cell surface or is secreted to facilitate pathogenesis. In many pathogenic bacteria, such as Streptococcus and Mycobacterium species, extracellular GAPDH acts as an adhesin by binding to host extracellular matrix components like fibronectin and plasminogen, thereby promoting tissue invasion and dissemination. It also contributes to immune evasion by modulating host inflammatory responses and inhibiting complement components like C5a. Due to its essentiality in bacterial energy metabolism and its multifaceted roles in virulence, GAPDH is considered a promising target for novel antimicrobial therapies, including small-molecule inhibitors and vaccines. However, the high degree of structural conservation between bacterial and human GAPDH poses a significant challenge for achieving therapeutic selectivity and avoiding host toxicity.

Other names

G3PDHGAPDGapAGlyceraldehyde-3-phosphate dehydrogenase (phosphorylating)Moonlighting GAPDH

Inhibition of the catalytic activity of the enzyme to disrupt bacterial glycolysis and neutralization of surface-associated GAPDH to prevent host cell adhesion and immune modulation.