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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1mfp

E.C. nameenoyl-[acyl-carrier-protein] reductase (NADH)
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz) 1.3.1.9
CSA Homologues of 1mfpThere are 413 Homologs
CSA Entries With UniProtID P0AEK4
CSA Entries With EC Number 1.3.1.9
PDBe Entry 1mfp
PDBSum Entry 1mfp
MACiE Entry 1mfp

Literature Report

IntroductionFabI catalyses the final step of fatty acid biosynthesis. Therefore it is a potential target for antibacterial agent development. It catalyses the NAD(P)H-dependent reduction of enoyl acyl carrier protein. EACPR's show homology, and similarity to hydroxysteroid dehydrogenase, and also beta-keto reductase, suggesting divergent evolution has played a role in the development of the pathway of lipid biosynthesis.
MechansimThe catalytic mechanism involves C3 of the substrate being subject to hydride attack by NADH, a bound cofactor. Formation of an enolate intermediate follows, which accepts a proton from Tyr 156. A role in transition state stabilisation through hydrogen bonding has also been suggested for Tyr 156. The enol product would then tautomerise to give the reduced acyl product. Tyr 156 therefore acts as the base that donates the proton to the enolate anion, and Lys 163 acts to stabilise the negatively charged transition state.
Reaction

Catalytic Sites for 1mfp

Annotated By Reference To The Literature - Site 3 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
TyrA156156macie:sideChainTyr 156 acts as the base that donates the proton to the enolate anion.
LysA163163macie:sideChainLys 163 acts to stabilise the negatively charged transition state.

Annotated By Reference To The Literature - Site 4 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
LysB1163163macie:sideChainLys 163 acts to stabilise the negatively charged transition state.
TyrB1156156macie:sideChainTyr 156 acts as the base that donates the proton to the enolate anion.

Literature References

Notes:
Parikh S
Roles of tyrosine 158 and lysine 165 in the catalytic mechanism of InhA, the enoyl-ACP reductase from Mycobacterium tuberculosis.
Biochemistry 1999 38 13623-13634
PubMed: 10521269
Seefeld MA
Indole naphthyridinones as inhibitors of bacterial enoyl-ACP reductases FabI and FabK.
J Med Chem 2003 46 1627-1635
PubMed: 12699381
Marcinkeviciene J
Enoyl-ACP reductase (FabI) of Haemophilus influenzae: steady-state kinetic mechanism and inhibition by triclosan and hexachlorophene.
Arch Biochem Biophys 2001 390 101-108
PubMed: 11368521
Ward WH
Kinetic and structural characteristics of the inhibition of enoyl (acyl carrier protein) reductase by triclosan.
Biochemistry 1999 38 12514-12525
PubMed: 10493822
Rafferty JB
Common themes in redox chemistry emerge from the X-ray structure of oilseed rape (Brassica napus) enoyl acyl carrier protein reductase.
Structure 1995 3 927-938
PubMed: 8535786
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