title: Epigallocatechin gallate is a slow-tight binding inhibitor of enoyl-ACP reductase from Plasmodium falciparum.
abstract: Epigallocatechin gallate (EGCG) is known to have numerous pharmacological properties. In the present study, we have shown that EGCG inhibits enoyl-acyl carrier protein reductase of Plasmodium falciparum (PfENR) by following a two-step, slow, tight-binding inhibition mechanism. The association/isomerization rate constant (k(5)) of the reversible and loose PfENR-EGCG binary complex to a tight [PfENR-EGCG](*) or EI(*) complex was calculated to be 4.0x10(-2) s(-1). The low dissociation rate constant (k(6)) of the [PfENR-EGCG](*) complex confirms the tight-binding nature of EGCG. EGCG inhibited PfENR with the overall inhibition constant (K(i)(*)) of 7.0+/-0.8 nM. Further, we also studied the effect of triclosan on the inhibitory activity of EGCG. Triclosan lowered the k(6) of the EI(*) complex by 100 times, lowering the overall K(i)(*) of EGCG to 97.5+/-12.5 pM. The results support EGCG as a promising candidate for the development of tea catechin based antimalarial drugs.
authors.affiliation: National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Tanushree
authors.initials: T
authors.lastname: Banerjee
authors.forename: Shailendra Kumar
authors.initials: SK
authors.lastname: Sharma
authors.forename: Namita
authors.initials: N
authors.lastname: Surolia
authors.forename: Avadhesha
authors.initials: A
authors.lastname: Surolia
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / Q000037:antagonists & inhibitors* / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000201:enzymology*; D014260:Triclosan / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D004791:Enzyme Inhibitors; D014260:Triclosan; D002392:Catechin; C045651:epigallocatechin gallate; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)