Plasmodium falciparum lactate dehydrogenase (PfLDH)

Plasmodium falciparum lactate dehydrogenase is an enzyme essential for the malaria parasite's anaerobic glycolytic metabolism within human erythrocytes, catalyzing the reduction of pyruvate to lactate while regenerating NAD+ needed for continued ATP production. Unlike human LDH, PfLDH evolved from malate dehydrogenase, possesses a unique five-residue active site loop, and includes specific structural features exploited for selective inhibitor design. Its critical role in parasite energy metabolism and the distinct active site make it an attractive antimalarial drug target; various inhibitors (e.g., gossypol, posaconazole) have shown experimental efficacy, though resistance and selectivity remain key concerns. PfLDH is also used as a biomarker for malaria diagnosis and monitoring response to treatment.

Other names

PfLDHLDH from Plasmodium falciparummalaria parasite LDH

Competitive inhibition of the LDH active site, blocking NADH binding or pyruvate reduction; Allosteric inhibition by binding distinct pockets unique to PfLDH; Specific inhibition of parasite over host homolog via parasite-specific active site loop