Enoyl-[acyl-carrier-protein] reductase [NADH] FabI

Details

Name
Enoyl-[acyl-carrier-protein] reductase [NADH] FabI
Synonyms
  • 1.3.1.9
  • ENR
  • envM
  • NADH-dependent enoyl-ACP reductase
Gene Name
fabI
Organism
Escherichia coli (strain K12)
Amino acid sequence
>lcl|BSEQ0011445|Enoyl-[acyl-carrier-protein] reductase [NADH] FabI
MGFLSGKRILVTGVASKLSIAYGIAQAMHREGAELAFTYQNDKLKGRVEEFAAQLGSDIV
LQCDVAEDASIDTMFAELGKVWPKFDGFVHSIGFAPGDQLDGDYVNAVTREGFKIAHDIS
SYSFVAMAKACRSMLNPGSALLTLSYLGAERAIPNYNVMGLAKASLEANVRYMANAMGPE
GVRVNAISAGPIRTLAASGIKDFRKMLAHCEAVTPIRRTVTIEDVGNSAAFLCSDLSAGI
SGEVVHVDGGFSIAAMNELELK
Number of residues
262
Molecular Weight
27863.645
Theoretical pI
5.67
GO Classification
Functions
enoyl-[acyl-carrier-protein] reductase (NADH) activity / identical protein binding
Processes
biotin biosynthetic process / fatty acid elongation / lipid biosynthetic process / protein homotetramerization / response to antibiotic
Components
cytosol / membrane
General Function
Identical protein binding
Specific 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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cell inner membrane; peripheral membrane protein
Gene sequence
>lcl|BSEQ0011446|Enoyl-[acyl-carrier-protein] reductase [NADH] FabI (fabI)
ATGGGTTTTCTTTCCGGTAAGCGCATTCTGGTAACCGGTGTTGCCAGCAAACTATCCATC
GCCTACGGTATCGCTCAGGCGATGCACCGCGAAGGAGCTGAACTGGCATTCACCTACCAG
AACGACAAACTGAAAGGCCGCGTAGAAGAATTTGCCGCTCAATTGGGTTCTGACATCGTT
CTGCAGTGCGATGTTGCAGAAGATGCCAGCATCGACACCATGTTCGCTGAACTGGGGAAA
GTTTGGCCGAAATTTGACGGTTTCGTACACTCTATTGGTTTTGCACCTGGCGATCAGCTG
GATGGTGACTATGTTAACGCCGTTACCCGTGAAGGCTTCAAAATTGCCCACGACATCAGC
TCCTACAGCTTCGTTGCAATGGCAAAAGCTTGCCGCTCCATGCTGAATCCGGGTTCTGCC
CTGCTGACCCTTTCCTACCTTGGCGCTGAGCGCGCTATCCCGAACTACAACGTTATGGGT
CTGGCAAAAGCGTCTCTGGAAGCGAACGTGCGCTATATGGCGAACGCGATGGGTCCGGAA
GGTGTGCGTGTTAACGCCATCTCTGCTGGTCCGATCCGTACTCTGGCGGCCTCCGGTATC
AAAGACTTCCGCAAAATGCTGGCTCATTGCGAAGCCGTTACCCCGATTCGCCGTACCGTT
ACTATTGAAGATGTGGGTAACTCTGCGGCATTCCTGTGCTCCGATCTCTCTGCCGGTATC
TCCGGTGAAGTGGTCCACGTTGACGGCGGTTTCAGCATTGCTGCAATGAACGAACTCGAA
CTGAAATAA
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP0AEK4
UniProtKB Entry NameFABI_ECOLI
GenBank Protein ID587106
GenBank Gene IDX78733
General References
  1. Bergler H, Hogenauer G, Turnowsky F: Sequences of the envM gene and of two mutated alleles in Escherichia coli. J Gen Microbiol. 1992 Oct;138(10):2093-100. [Article]
  2. Kater MM, Koningstein GM, Nijkamp HJ, Stuitje AR: The use of a hybrid genetic system to study the functional relationship between prokaryotic and plant multi-enzyme fatty acid synthetase complexes. Plant Mol Biol. 1994 Aug;25(5):771-90. [Article]
  3. Aiba H, Baba T, 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, Nakade S, Nakamura Y, Nashimoto H, Nishio Y, Oshima T, Saito N, Sampei G, Horiuchi T, et al.: 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. DNA Res. 1996 Dec 31;3(6):363-77. [Article]
  4. Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453-62. [Article]
  5. Hayashi K, Morooka N, Yamamoto Y, Fujita K, Isono K, Choi S, Ohtsubo E, Baba T, Wanner BL, Mori H, Horiuchi T: Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110. Mol Syst Biol. 2006;2:2006.0007. Epub 2006 Feb 21. [Article]
  6. Bergler H, Wallner P, Ebeling A, Leitinger B, Fuchsbichler S, Aschauer H, Kollenz G, Hogenauer G, Turnowsky F: Protein EnvM is the NADH-dependent enoyl-ACP reductase (FabI) of Escherichia coli. J Biol Chem. 1994 Feb 25;269(8):5493-6. [Article]
  7. Link AJ, Robison K, Church GM: Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K-12. Electrophoresis. 1997 Aug;18(8):1259-313. [Article]
  8. Heath RJ, Rock CO: Enoyl-acyl carrier protein reductase (fabI) plays a determinant role in completing cycles of fatty acid elongation in Escherichia coli. J Biol Chem. 1995 Nov 3;270(44):26538-42. [Article]
  9. McMurry LM, Oethinger M, Levy SB: Triclosan targets lipid synthesis. Nature. 1998 Aug 6;394(6693):531-2. [Article]
  10. Yao J, Zhang Q, Min J, He J, Yu Z: Novel enoyl-ACP reductase (FabI) potential inhibitors of Escherichia coli from Chinese medicine monomers. Bioorg Med Chem Lett. 2010 Jan 1;20(1):56-9. doi: 10.1016/j.bmcl.2009.11.042. Epub 2009 Nov 14. [Article]
  11. Lin S, Hanson RE, Cronan JE: Biotin synthesis begins by hijacking the fatty acid synthetic pathway. Nat Chem Biol. 2010 Sep;6(9):682-8. doi: 10.1038/nchembio.420. Epub 2010 Aug 8. [Article]
  12. Baldock C, Rafferty JB, Sedelnikova SE, Baker PJ, Stuitje AR, Slabas AR, Hawkes TR, Rice DW: A mechanism of drug action revealed by structural studies of enoyl reductase. Science. 1996 Dec 20;274(5295):2107-10. [Article]
  13. Ward WH, Holdgate GA, Rowsell S, McLean EG, Pauptit RA, Clayton E, Nichols WW, Colls JG, Minshull CA, Jude DA, Mistry A, Timms D, Camble R, Hales NJ, Britton CJ, Taylor IW: Kinetic and structural characteristics of the inhibition of enoyl (acyl carrier protein) reductase by triclosan. Biochemistry. 1999 Sep 21;38(38):12514-25. [Article]
  14. Stewart MJ, Parikh S, Xiao G, Tonge PJ, Kisker C: Structural basis and mechanism of enoyl reductase inhibition by triclosan. J Mol Biol. 1999 Jul 23;290(4):859-65. [Article]
  15. Levy CW, Roujeinikova A, Sedelnikova S, Baker PJ, Stuitje AR, Slabas AR, Rice DW, Rafferty JB: Molecular basis of triclosan activity. Nature. 1999 Apr 1;398(6726):383-4. [Article]
  16. Qiu X, Janson CA, Court RI, Smyth MG, Payne DJ, Abdel-Meguid SS: Molecular basis for triclosan activity involves a flipping loop in the active site. Protein Sci. 1999 Nov;8(11):2529-32. [Article]
  17. Heerding DA, Chan G, DeWolf WE, Fosberry AP, Janson CA, Jaworski DD, McManus E, Miller WH, Moore TD, Payne DJ, Qiu X, Rittenhouse SF, Slater-Radosti C, Smith W, Takata DT, Vaidya KS, Yuan CC, Huffman WF: 1,4-Disubstituted imidazoles are potential antibacterial agents functioning as inhibitors of enoyl acyl carrier protein reductase (FabI). Bioorg Med Chem Lett. 2001 Aug 20;11(16):2061-5. [Article]
  18. Miller WH, Seefeld MA, Newlander KA, Uzinskas IN, Burgess WJ, Heerding DA, Yuan CC, Head MS, Payne DJ, Rittenhouse SF, Moore TD, Pearson SC, Berry V, DeWolf WE Jr, Keller PM, Polizzi BJ, Qiu X, Janson CA, Huffman WF: Discovery of aminopyridine-based inhibitors of bacterial enoyl-ACP reductase (FabI). J Med Chem. 2002 Jul 18;45(15):3246-56. [Article]
  19. Seefeld MA, Miller WH, Newlander KA, Burgess WJ, DeWolf WE Jr, Elkins PA, Head MS, Jakas DR, Janson CA, Keller PM, Manley PJ, Moore TD, Payne DJ, Pearson S, Polizzi BJ, Qiu X, Rittenhouse SF, Uzinskas IN, Wallis NG, Huffman WF: Indole naphthyridinones as inhibitors of bacterial enoyl-ACP reductases FabI and FabK. J Med Chem. 2003 Apr 24;46(9):1627-35. [Article]
  20. Rafi S, Novichenok P, Kolappan S, Zhang X, Stratton CF, Rawat R, Kisker C, Simmerling C, Tonge PJ: Structure of acyl carrier protein bound to FabI, the FASII enoyl reductase from Escherichia coli. J Biol Chem. 2006 Dec 22;281(51):39285-93. Epub 2006 Sep 29. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01691Indole NaphthyridinoneexperimentalunknownDetails
DB018653-(6-Aminopyridin-3-Yl)-N-Methyl-N-[(1-Methyl-1h-Indol-2-Yl)Methyl]AcrylamideexperimentalunknownDetails
DB030304-(2-Thienyl)-1-(4-Methylbenzyl)-1h-ImidazoleexperimentalunknownDetails
DB035343-[(Acetyl-Methyl-Amino)-Methyl]-4-Amino-N-Methyl-N-(1-Methyl-1h-Indol-2-Ylmethyl)-BenzamideexperimentalunknownDetails
DB040301,3,4,9-Tetrahydro-2-(Hydroxybenzoyl)-9-[(4-Hydroxyphenyl)Methyl]-6-Methoxy-2h-Pyrido[3,4-B]IndoleexperimentalunknownDetails
DB02379Beta-D-GlucoseexperimentalunknownDetails
DB082652-(TOLUENE-4-SULFONYL)-2H-BENZO[D][1,2,3]DIAZABORININ-1-OLexperimentalunknownDetails
DB08604Triclosanapproved, investigationalunknownDetails
DB086056-METHYL-2(PROPANE-1-SULFONYL)-2H-THIENO[3,2-D][1,2,3]DIAZABORININ-1-OLexperimentalunknownDetails