General Information of the Molecule (ID: Mol01022)
Name
NADH-dependent enoyl-ACP reductase (FABL) ,Escherichia coli
Synonyms
ENR; NADH-dependent enoyl-ACP reductase; envM; b1288; JW1281
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Molecule Type
Protein
Gene Name
fabI
Gene ID
67417387
Sequence
MGFLSGKRILVTGVASKLSIAYGIAQAMHREGAELAFTYQNDKLKGRVEEFAAQLGSDIV
LQCDVAEDASIDTMFAELGKVWPKFDGFVHSIGFAPGDQLDGDYVNAVTREGFKIAHDIS
SYSFVAMAKACRSMLNPGSALLTLSYLGAERAIPNYNVMGLAKASLEANVRYMANAMGPE
GVRVNAISAGPIRTLAASGIKDFRKMLAHCEAVTPIRRTVTIEDVGNSAAFLCSDLSAGI
SGEVVHVDGGFSIAAMNELELK
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Function
Catalyzes the reduction of a carbon-carbon double bond in an enoyl moiety that is covalently linked to an acyl carrier protein (ACP). Involved in the elongation cycle of fatty acid which are used in the lipid metabolism and in the biotin biosynthesis.
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Uniprot ID
FABI_ECOLI
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Kingdom: N.A.
Phylum: Proteobacteria
Class: Gammaproteobacteria
Order: Enterobacterales
Family: Enterobacteriaceae
Genus: Escherichia
Species: Escherichia coli
Type(s) of Resistant Mechanism of This Molecule
  ADTT: Aberration of the Drug's Therapeutic Target
Drug Resistance Data Categorized by Drug
Approved Drug(s)
1 drug(s) in total
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Triclosan
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Escherichia coli infection [1]
Resistant Disease Escherichia coli infection [ICD-11: 1A03.0]
Resistant Drug Triclosan
Molecule Alteration Missense mutation
p.G93V
Experimental Note Discovered Using In-vivo Testing Model
In Vitro Model E. coli IFN4 562
E. coli imp4231 FabI(G93V) strain 562
Experiment for
Drug Resistance
MIC assay
Mechanism Description Among the triclosan-resistant mutants, E. coli AGT11, which had a Gly93 Val mutation in fabI, FabI(G93V), showed a 95-fold higher MIC than the wild-type. On the basis of these results, Levy et al.7 carried out structural analysis and inhibition experiments on a complex of E. coli FabI with triclosan and NAD+ and found that a FabI NAD+ triclosan ternary complex was formed by face-to-face interaction between the phenol ring of triclosan and the nicotinamide ring of NAD+ in the active site of FabI. In contrast to intact FabI, overexpression of FabI(G93V) conferred greater triclosan resistance by preventing formation of the FabI NAD+ triclosan ternary complex.
References
Ref 1 Signature gene expression profile of triclosan-resistant Escherichia coli. J Antimicrob Chemother. 2010 Jun;65(6):1171-7. doi: 10.1093/jac/dkq114. Epub 2010 Apr 21.

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