Pantothenate synthetase (PS)

Pantothenate synthetase is an enzyme (EC 6.3.2.1) that catalyzes the final, ATP-dependent step in the biosynthesis of pantothenate (vitamin B5) from pantoate and β-alanine via a pantoyl-adenylate intermediate[1][2][6]. It is crucial for the survival of bacteria, fungi, and plants, which synthesize pantothenate de novo, unlike animals that require dietary intake of the vitamin. The enzyme is structurally characterized by a dimeric organization with each monomer possessing a Rossmann-fold N-terminal domain and a C-terminal domain, and it belongs to the cytidylyltransferase superfamily[1][2]. Pantothenate synthetase is a validated antimicrobial drug target, particularly in Mycobacterium tuberculosis, because disruption of the pathway is lethal to the pathogen without affecting human cells[4][2]. Inhibition mechanisms include structural mimics of transition states or intermediates, informing recent antitubercular drug research. The broad substrate scope of bacterial pantothenate synthetase has been exploited for the synthetic production of vitamin B5 derivatives and assessment of enzyme promiscuity in biocatalysis[5].

Other names

PanCPantoate—beta-alanine ligaseVitamin B5 synthetase

Competitive inhibition at the ATP or pantoate/β-alanine binding sites Inhibition by analogues of the pantoyl-adenylate reaction intermediate[4]