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P0AEK4 (FABI_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 86. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Enoyl-[acyl-carrier-protein] reductase [NADH] FabI

Short name=ENR
EC=1.3.1.9
Alternative name(s):
NADH-dependent enoyl-ACP reductase
Gene names
Name:fabI
Synonyms:envM
Ordered Locus Names:b1288, JW1281
OrganismEscherichia coli (strain K12) [Reference proteome] [HAMAP]
Taxonomic identifier83333 [NCBI]
Taxonomic lineageBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia

Protein attributes

Sequence length262 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.6 Ref.9 Ref.12

Catalytic activity

An acyl-[acyl-carrier protein] + NAD+ = a trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH. Ref.6

Enzyme regulation

Inhibited by diazaborines, triclosan (5-chloro-2-2,4-dichlorophenoxyphenol), 1,4-disubstituted imidazoles, 1,4-benzodiazepine derivatives, naphthyridinone derivatives, luteolin and curcumin. Ref.6 Ref.10 Ref.11 Ref.13 Ref.14 Ref.15 Ref.18 Ref.19 Ref.20

Pathway

Lipid metabolism; fatty acid biosynthesis.

Cofactor biosynthesis; biotin biosynthesis.

Subunit structure

Homotetramer. Ref.13 Ref.14 Ref.15

Miscellaneous

The antibiotic diazaborine interferes with the activity by binding to the protein and NAD.

Sequence similarities

Belongs to the short-chain dehydrogenases/reductases (SDR) family. FabI subfamily.

Biophysicochemical properties

Kinetic parameters:

KM=3.3 µM for trans-2-dodecenoyl-ACP (DD-ACP)(at 25 degrees Celsius and pH 8) Ref.6 Ref.21

KM=22 µM for crotonyl-ACP (at 30 degrees Celsius and pH 7.5)

KM=24 µM for trans-2-dodecenoyl-CoA (DD-CoA)(at 25 degrees Celsius and pH 8)

KM=2700 µM for crotonyl-CoA (at 30 degrees Celsius and pH 7.5)

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.1 Ref.7 Ref.8
Chain2 – 262261Enoyl-[acyl-carrier-protein] reductase [NADH] FabI
PRO_0000054899

Regions

Nucleotide binding19 – 202NAD
Nucleotide binding64 – 652NAD
Nucleotide binding192 – 1965NAD

Sites

Active site1461Proton acceptor By similarity
Active site1561Proton acceptor By similarity
Binding site131NAD; via carbonyl oxygen
Binding site401NAD
Binding site921NAD; via carbonyl oxygen
Binding site951Substrate; via amide nitrogen and carbonyl oxygen
Binding site1631NAD
Site2011Involved in acyl-ACP binding
Site2041Involved in acyl-ACP binding
Site2051Involved in acyl-ACP binding

Experimental info

Mutagenesis931G → S: Diazaborine resistance. Ref.1 Ref.10
Mutagenesis931G → V: Triclosan resistance. Ref.1 Ref.10
Mutagenesis1461Y → F: Large impact on catalysis, with kcat and kcat/Km for DD-ACP decreasing by around 50-fold compared with wild-type. Ref.21
Mutagenesis1561Y → F: No effect on substrate reduction. Ref.21
Mutagenesis1591M → T: Triclosan resistance. Ref.10
Mutagenesis2011K → A: No effect on substrate reduction. Ref.21
Mutagenesis2011K → E: Little activity toward DD-CoA and DD-ACP. Ref.21
Mutagenesis2031F → L: Triclosan resistance. Ref.10
Mutagenesis2041R → A: No effect on substrate reduction. Ref.21
Mutagenesis2041R → E: Causes a further reduction in kcat/Km for reduction of DD-ACP without affecting kcat/Km for the DD-CoA substrate. Ref.21
Mutagenesis2051K → A: No effect on substrate reduction. Ref.21
Mutagenesis2051K → E: Causes a further reduction in kcat/Km for reduction of DD-ACP without affecting kcat/Km for the DD-CoA substrate. Has a larger impact on substrate reduction. Ref.21
Mutagenesis2411S → F: Produces temperature-sensitive phenotype.

Secondary structure

............................................... 262
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P0AEK4 [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: 436A89AF349D1866

FASTA26227,864
        10         20         30         40         50         60 
MGFLSGKRIL VTGVASKLSI AYGIAQAMHR EGAELAFTYQ NDKLKGRVEE FAAQLGSDIV 

        70         80         90        100        110        120 
LQCDVAEDAS IDTMFAELGK VWPKFDGFVH SIGFAPGDQL DGDYVNAVTR EGFKIAHDIS 

       130        140        150        160        170        180 
SYSFVAMAKA CRSMLNPGSA LLTLSYLGAE RAIPNYNVMG LAKASLEANV RYMANAMGPE 

       190        200        210        220        230        240 
GVRVNAISAG PIRTLAASGI KDFRKMLAHC EAVTPIRRTV TIEDVGNSAA FLCSDLSAGI 

       250        260 
SGEVVHVDGG FSIAAMNELE LK 

« Hide

References

« Hide 'large scale' references
[1]"Sequences of the envM gene and of two mutated alleles in Escherichia coli."
Bergler H., Hoegenauer G., Turnowsky F.
J. Gen. Microbiol. 138:2093-2100(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-31, MUTAGENESIS OF GLY-93.
[2]"The use of a hybrid genetic system to study the functional relationship between prokaryotic and plant multi-enzyme fatty acid synthetase complexes."
Kater M.M., Koningstein G.M., Nijkamp H.J.J., Stuitje A.R.
Plant Mol. Biol. 25:771-790(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[3]"A 570-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 28.0-40.1 min region on the linkage map."
Aiba H., Baba T., Fujita K., Hayashi K., Inada T., Isono K., Itoh T., Kasai H., Kashimoto K., Kimura S., Kitakawa M., Kitagawa M., Makino K., Miki T., Mizobuchi K., Mori H., Mori T., Motomura K. expand/collapse author list , Nakade S., Nakamura Y., Nashimoto H., Nishio Y., Oshima T., Saito N., Sampei G., Seki Y., Sivasundaram S., Tagami H., Takeda J., Takemoto K., Takeuchi Y., Wada C., Yamamoto Y., Horiuchi T.
DNA Res. 3:363-377(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[4]"The complete genome sequence of Escherichia coli K-12."
Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., Shao Y.
Science 277:1453-1462(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / MG1655 / ATCC 47076.
[5]"Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110."
Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.
Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[6]"Protein EnvM is the NADH-dependent enoyl-ACP reductase (FabI) of Escherichia coli."
Bergler H., Wallner P., Ebeling A., Leitinger B., Fuchsbichler S., Aschauer H., Kollenz G., Hoegenauer G., Turnowsky F.
J. Biol. Chem. 269:5493-5496(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE, FUNCTION AS AN ENOYL-ACP REDUCTASE, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, COFACTOR.
[7]"Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K-12."
Link A.J., Robison K., Church G.M.
Electrophoresis 18:1259-1313(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-13.
Strain: K12 / EMG2.
[8]Frutiger S., Hughes G.J., Pasquali C., Hochstrasser D.F.
Submitted (FEB-1996) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-12.
Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[9]"Enoyl-acyl carrier protein reductase (fabI) plays a determinant role in completing cycles of fatty acid elongation in Escherichia coli."
Heath R.J., Rock C.O.
J. Biol. Chem. 270:26538-26542(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN FATTY ACID BIOSYNTHESIS.
[10]"Triclosan targets lipid synthesis."
McMurry L.M., Oethinger M., Levy S.B.
Nature 394:531-532(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, MUTAGENESIS OF GLY-93; MET-159 AND PHE-203.
[11]"Novel enoyl-ACP reductase (FabI) potential inhibitors of Escherichia coli from Chinese medicine monomers."
Yao J., Zhang Q., Min J., He J., Yu Z.
Bioorg. Med. Chem. Lett. 20:56-59(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[12]"Biotin synthesis begins by hijacking the fatty acid synthetic pathway."
Lin S., Hanson R.E., Cronan J.E.
Nat. Chem. Biol. 6:682-688(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN BIOTIN BIOSYNTHESIS.
[13]"A mechanism of drug action revealed by structural studies of enoyl reductase."
Baldock C., Rafferty J.B., Sedelnikova S.E., Baker P.J., Stuitje A.R., Slabas A.R., Hawkes T.R., Rice D.W.
Science 274:2107-2110(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH NAD AND INHIBITOR, ENZYME REGULATION, SUBUNIT.
[14]"Kinetic and structural characteristics of the inhibition of enoyl (acyl carrier protein) reductase by triclosan."
Ward W.H., Holdgate G.A., Rowsell S., McLean E.G., Pauptit R.A., Clayton E., Nichols W.W., Colls J.G., Minshull C.A., Jude D.A., Mistry A., Timms D., Camble R., Hales N.J., Britton C.J., Taylor I.W.
Biochemistry 38:12514-12525(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH NAD AND INHIBITOR, ENZYME REGULATION, SUBUNIT.
[15]"Structural basis and mechanism of enoyl reductase inhibition by triclosan."
Stewart M.J., Parikh S., Xiao G., Tonge P.J., Kisker C.
J. Mol. Biol. 290:859-865(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEX WITH NAD AND INHIBITOR, ENZYME REGULATION, SUBUNIT.
[16]"Molecular basis of triclosan activity."
Levy C.W., Roujeinikova A., Sedelnikova S., Baker P.J., Stuitje A.R., Slabas A.R., Rice D.W., Rafferty J.B.
Nature 398:383-384(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH NAD AND INHIBITOR.
[17]"Molecular basis for triclosan activity involves a flipping loop in the active site."
Qiu X., Janson C.A., Court R.I., Smyth M.G., Payne D.J., Abdel-Meguid S.S.
Protein Sci. 8:2529-2532(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH NAD AND INHIBITOR.
[18]"1,4-Disubstituted imidazoles are potential antibacterial agents functioning as inhibitors of enoyl acyl carrier protein reductase (FabI)."
Heerding D.A., Chan G., DeWolf W.E., Fosberry A.P., Janson C.A., Jaworski D.D., McManus E., Miller W.H., Moore T.D., Payne D.J., Qiu X., Rittenhouse S.F., Slater-Radosti C., Smith W., Takata D.T., Vaidya K.S., Yuan C.C., Huffman W.F.
Bioorg. Med. Chem. Lett. 11:2061-2065(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH NAD AND INHIBITOR, ENZYME REGULATION.
[19]"Discovery of aminopyridine-based inhibitors of bacterial enoyl-ACP reductase (FabI)."
Miller W.H., Seefeld M.A., Newlander K.A., Uzinskas I.N., Burgess W.J., Heerding D.A., Yuan C.C., Head M.S., Payne D.J., Rittenhouse S.F., Moore T.D., Pearson S.C., Berry V., DeWolf W.E. Jr., Keller P.M., Polizzi B.J., Qiu X., Janson C.A., Huffman W.F.
J. Med. Chem. 45:3246-3256(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH NAD AND INHIBITOR, ENZYME REGULATION.
[20]"Indole naphthyridinones as inhibitors of bacterial enoyl-ACP reductases FabI and FabK."
Seefeld M.A., Miller W.H., Newlander K.A., Burgess W.J., DeWolf W.E. Jr., Elkins P.A., Head M.S., Jakas D.R., Janson C.A., Keller P.M., Manley P.J., Moore T.D., Payne D.J., Pearson S., Polizzi B.J., Qiu X., Rittenhouse S.F., Uzinskas I.N., Wallis N.G., Huffman W.F.
J. Med. Chem. 46:1627-1635(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.33 ANGSTROMS) IN COMPLEX WITH NAD AND INHIBITOR, ENZYME REGULATION.
[21]"Structure of acyl carrier protein bound to FabI, the FASII enoyl reductase from Escherichia coli."
Rafi S., Novichenok P., Kolappan S., Zhang X., Stratton C.F., Rawat R., Kisker C., Simmerling C., Tonge P.J.
J. Biol. Chem. 281:39285-39293(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS), MUTAGENESIS OF TYR-146; TYR-156; LYS-201; ARG-204 AND LYS-205, BIOPHYSICOCHEMICAL PROPERTIES.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M97219 Unassigned DNA. Translation: AAA17755.1.
X78733 Genomic DNA. Translation: CAA55381.1.
U00096 Genomic DNA. Translation: AAC74370.1.
AP009048 Genomic DNA. Translation: BAA14841.1.
PIRS48029.
RefSeqNP_415804.1. NC_000913.3.
YP_489556.1. NC_007779.1.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1C14X-ray2.00A/B1-262[»]
1D8AX-ray2.20A/B2-262[»]
1DFGX-ray2.50A/B2-262[»]
1DFHX-ray2.20A/B2-262[»]
1DFIX-ray2.09A/B/C/D2-262[»]
1I2ZX-ray2.80A/B1-262[»]
1I30X-ray2.40A/B1-262[»]
1LX6X-ray2.40A/B1-262[»]
1LXCX-ray2.40A/B1-262[»]
1MFPX-ray2.33A/B1-262[»]
1QG6X-ray1.90A/B/C/D2-262[»]
1QSGX-ray1.75A/B/C/D/E/F/G/H1-262[»]
2FHSX-ray2.70A/B1-262[»]
3PJDX-ray2.50A/B1-262[»]
3PJEX-ray2.50A/B1-262[»]
3PJFX-ray1.90A/B1-262[»]
ProteinModelPortalP0AEK4.
SMRP0AEK4. Positions 2-260.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-31867N.
IntActP0AEK4. 12 interactions.
MINTMINT-1251203.
STRING511145.b1288.

Chemistry

BindingDBP0AEK4.
ChEMBLCHEMBL1857.

2D gel databases

SWISS-2DPAGEP0AEK4.

Proteomic databases

PaxDbP0AEK4.
PRIDEP0AEK4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaAAC74370; AAC74370; b1288.
BAA14841; BAA14841; BAA14841.
GeneID12931141.
945870.
KEGGecj:Y75_p1263.
eco:b1288.
PATRIC32117844. VBIEscCol129921_1342.

Organism-specific databases

EchoBASEEB1490.
EcoGeneEG11528. fabI.

Phylogenomic databases

eggNOGCOG0623.
KOK00208.
OMADCDVGSD.
OrthoDBEOG6HF644.
PhylomeDBP0AEK4.
ProtClustDBPRK07984.

Enzyme and pathway databases

BioCycEcoCyc:ENOYL-ACP-REDUCT-NADH-MONOMER.
ECOL316407:JW1281-MONOMER.
MetaCyc:ENOYL-ACP-REDUCT-NADH-MONOMER.
SABIO-RKP0AEK4.
UniPathwayUPA00078.
UPA00094.

Gene expression databases

GenevestigatorP0AEK4.

Family and domain databases

Gene3D3.40.50.720. 1 hit.
InterProIPR014358. Enoyl-ACP_Rdtase_NADH.
IPR002347. Glc/ribitol_DH.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PIRSFPIRSF000094. Enoyl-ACP_rdct. 1 hit.
PRINTSPR00081. GDHRDH.
ProtoNetSearch...

Other

EvolutionaryTraceP0AEK4.
PROP0AEK4.

Entry information

Entry nameFABI_ECOLI
AccessionPrimary (citable) accession number: P0AEK4
Secondary accession number(s): P29132
Entry history
Integrated into UniProtKB/Swiss-Prot: December 20, 2005
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 86 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

Escherichia coli

Escherichia coli (strain K12): entries and cross-references to EcoGene