Protein EnvM is the NADH-dependent enoyl-ACP reductase (FabI) of Escherichia coli.

Crystal structures of substrate binding to Bacillus subtilis holo-(acyl carrier protein) synthase reveal a novel trimeric arrangement of molecules resulting in three active sites

“…The Escherichia coli ACP for fatty acid synthesis has been over-expressed [10], purified [11,12], and the low-resolution solution structure solved using nuclear magnetic resonance (NMR) spectroscopy [13]. The fact that these proteins are essential for the maturation of the organism has led to their investigation as targets for the development of new antimicrobial agents [14][15][16][17][18].…”

Structural basis for inhibition of the AAA-ATPase Drg1 by diazaborine

“…2c ). This covalent diazaborine-nucleotide adduct is reminiscent of a similar adduct formed by diazaborine and NAD + in the enoyl-acyl carrier protein reductase FabI, the bacterial target of diazaborine 30 – 32 . The bipartite density of the inhibitor moiety inside the Drg1 D2 domain strongly resembles the electron density of diazaborine bound to the bacterial protein in the crystal structure of FabI 31 , with the difference that the aliphatic chain is not clearly resolved in our structure due to the predicted orientational flexibility of this part of the inhibitor (Supplementary Fig.…”

“…Although this diazaborine derivative specifically targets Drg1 in yeast, there is also a known target of this compound in prokaryotes. The chemical class of diazaborines was originally investigated as a new group of antibacterial agents since they proved to be active against the Enoyl-ACP reductase (FabI) of Escherichia coli and other Gram-negative bacteria 25 , 30 , 31 . Since FabI belongs to the short-chain alcohol dehydrogenase family and is involved in bacterial fatty acid synthesis, it shares no conserved function or extensive structural similarity with Drg1, except that both are nucleotide utilizing enzymes (NADH for FabI and ATP for Drg1).…”

“…Since FabI belongs to the short-chain alcohol dehydrogenase family and is involved in bacterial fatty acid synthesis, it shares no conserved function or extensive structural similarity with Drg1, except that both are nucleotide utilizing enzymes (NADH for FabI and ATP for Drg1). Diazaborine inhibits both targets by forming a covalently linked adduct with the nucleotide and can thus only bind when the binding pocket is loaded with ATP or NAD + 21 , 30 . Covalent bond formation is driven by the high reactivity of the boronic acid group 31 , 32 , 40 .…”

Theoretical design of novel antimalarial agents against P. falciparum strain, Dd2 through the QSAR modeling of synthesized 2′-substituted triclosan derivatives

“…The α, β-unsaturated fatty acids double bonds bonded to the acyl carrier protein (ACP) in an NADH or NADPH based reaction were decreased by Enoyl-ACP (acyl carrier protein)-reductase (FabI) [10,11]. Triclosan, reported to strikingly inhibit its FabI target [12,13,14,15] binds straight to the P. falciparum FabI, which enhanced its affinity for the oxidized form of the co-factor NADþ and therefore confining the protein in its NAD-bound form.…”