Slow-tight-binding inhibition of enoyl-acyl carrier protein reductase from Plasmodium falciparum by triclosan.

@article{Kapoor2004SlowtightbindingIO,
  title={Slow-tight-binding inhibition of enoyl-acyl carrier protein reductase from Plasmodium falciparum by triclosan.},
  author={Mili Kapoor and C. C. Reddy and Musti V. Krishnasastry and Namita Surolia and Avadhesha Surolia},
  journal={The Biochemical journal},
  year={2004},
  volume={381 Pt 3},
  pages={
          719-24
        }
}
Triclosan is a potent inhibitor of FabI (enoyl-ACP reductase, where ACP stands for acyl carrier protein), which catalyses the last step in a sequence of four reactions that is repeated many times with each elongation step in the type II fatty acid biosynthesis pathway. The malarial parasite Plasmodium falciparum also harbours the genes and is capable of synthesizing fatty acids by utilizing the enzymes of type II FAS (fatty acid synthase). The basic differences in the enzymes of type I FAS… Expand
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Crystal structures of pseudomonas aeruginosa Enoyl-ACP reductase (FabI) in the presence and absence of NAD+ and triclosan
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Kinetic determinants of the interaction of enoyl-ACP reductase from Plasmodium falciparum with its substrates and inhibitors.
TLDR
The initial characterization of Plasmodium FabI expressed in Escherichia coli is reported, which shows that the binding of triclosan to the enzyme is facilitated in the presence of NAD(+) and competitive kinetics with respect to NADH are shown. Expand
Structural Elucidation of the Specificity of the Antibacterial Agent Triclosan for Malarial Enoyl Acyl Carrier Protein Reductase*
TLDR
The cloning and expression of the P. falciparum enoyl acyl carrier protein reductase gene is reported, which encodes a 50-kDa protein (PfENR) predicted to target to the unique parasite apicoplast, and the structural basis of triclosan binding to PfENR is defined, which will facilitate structure-based optimization of Pf ENR inhibitors. Expand
Mutational analysis of the triclosan-binding region of enoyl-ACP (acyl-carrier protein) reductase from Plasmodium falciparum.
TLDR
Modelling studies and crystal structure studies point out significant differences in the triclosan-binding region of the P. falciparum enzyme from those of its bacterial counterparts. Expand
Kinetic and structural characteristics of the inhibition of enoyl (acyl carrier protein) reductase by triclosan.
TLDR
The results suggest that triclosan binds to E-NAD(+) complex, with a dissociation constant around 20-40 pM, which appears to be due to structural similarity to a tightly bound intermediate in catalysis. Expand
Inhibitor Binding Studies on Enoyl Reductase Reveal Conformational Changes Related to Substrate Recognition*
Enoyl acyl carrier protein reductase (ENR) is involved in fatty acid biosynthesis. In Escherichia colithis enzyme is the target for the experimental family of antibacterial agents, the diazaborines,Expand
Triclosan inhibits the growth of Plasmodium falciparum and Toxoplasma gondii by inhibition of apicomplexan Fab I.
TLDR
Discovery and characterisation of an apicomplexan Fab I and discovery of triclosan as lead compound provide means to rationally design novel inhibitory compounds. Expand
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TLDR
Investigation of the structures of complexes of Escherichia coli enoyl-ACP reductase from crystals grown in the presence of NAD+ and a family of diazaborine compounds reveals how, for one of the ordered conformations adopted by the mobile loop, the mode of d Diazaborine binding correlates well with the activity profiles of the diazborine family. Expand
The Enoyl-[acyl-carrier-protein] Reductases FabI and FabL fromBacillus subtilis *
TLDR
YgaA was renamed FabL to denote the discovery of a new family of proteins that carry out the enoyl-ACP reductase step in type II fatty-acid synthases, which was as sensitive as the wild-type strain to triclosan whereas the ygaA knockout was 250-fold more sensitive to the drug. Expand
Inhibition of the Staphylococcus aureusNADPH-dependent Enoyl-Acyl Carrier Protein Reductase by Triclosan and Hexachlorophene*
TLDR
The formation of a stable FabI-NAD(P)+-drug ternary complex is a key determinant of the antibacterial activity of FabI inhibitors. Expand
Slow-Tight Binding Inhibition of Xylanase by an Aspartic Protease Inhibitor
TLDR
The results revealed that the inactivation ofXyl I is due to the disruption of the hydrogen-bonding network between the essential histidine and other residues involved in catalysis and a model depicting the probable interaction between ATBI or OPTA with Xyl I has been proposed. Expand
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