FABI_STAA8
ID FABI_STAA8 Reviewed; 256 AA.
AC Q2FZQ3;
DT 03-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 1.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Enoyl-[acyl-carrier-protein] reductase [NADPH] FabI;
DE Short=ENR;
DE EC=1.3.1.39;
DE AltName: Full=NADPH-dependent enoyl-ACP reductase;
GN Name=fabI; OrderedLocusNames=SAOUHSC_00947;
OS Staphylococcus aureus (strain NCTC 8325 / PS 47).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=93061;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NCTC 8325 / PS 47;
RA Gillaspy A.F., Worrell V., Orvis J., Roe B.A., Dyer D.W., Iandolo J.J.;
RT "The Staphylococcus aureus NCTC 8325 genome.";
RL (In) Fischetti V., Novick R., Ferretti J., Portnoy D., Rood J. (eds.);
RL Gram positive pathogens, 2nd edition, pp.381-412, ASM Press, Washington
RL D.C. (2006).
RN [2]
RP ACTIVITY REGULATION.
RC STRAIN=ATCC 9144 / Oxford / NCIB 6571 / NCTC 6571;
RX PubMed=11514139; DOI=10.1016/s0960-894x(01)00404-8;
RA Heerding D.A., Chan G., DeWolf W.E., Fosberry A.P., Janson C.A.,
RA Jaworski D.D., McManus E., Miller W.H., Moore T.D., Payne D.J., Qiu X.,
RA Rittenhouse S.F., Slater-Radosti C., Smith W., Takata D.T., Vaidya K.S.,
RA Yuan C.C., Huffman W.F.;
RT "1,4-Disubstituted imidazoles are potential antibacterial agents
RT functioning as inhibitors of enoyl acyl carrier protein reductase (FabI).";
RL Bioorg. Med. Chem. Lett. 11:2061-2065(2001).
RN [3]
RP ACTIVITY REGULATION.
RX PubMed=12109908; DOI=10.1021/jm020050+;
RA Miller W.H., Seefeld M.A., Newlander K.A., Uzinskas I.N., Burgess W.J.,
RA Heerding D.A., Yuan C.C., Head M.S., Payne D.J., Rittenhouse S.F.,
RA Moore T.D., Pearson S.C., Berry V., DeWolf W.E. Jr., Keller P.M.,
RA Polizzi B.J., Qiu X., Janson C.A., Huffman W.F.;
RT "Discovery of aminopyridine-based inhibitors of bacterial enoyl-ACP
RT reductase (FabI).";
RL J. Med. Chem. 45:3246-3256(2002).
RN [4]
RP ACTIVITY REGULATION.
RX PubMed=12699381; DOI=10.1021/jm0204035;
RA Seefeld M.A., Miller W.H., Newlander K.A., Burgess W.J., DeWolf W.E. Jr.,
RA Elkins P.A., Head M.S., Jakas D.R., Janson C.A., Keller P.M., Manley P.J.,
RA Moore T.D., Payne D.J., Pearson S., Polizzi B.J., Qiu X., Rittenhouse S.F.,
RA Uzinskas I.N., Wallis N.G., Huffman W.F.;
RT "Indole naphthyridinones as inhibitors of bacterial enoyl-ACP reductases
RT FabI and FabK.";
RL J. Med. Chem. 46:1627-1635(2003).
RN [5]
RP FUNCTION AS AN ENOYL-ACP REDUCTASE, MUTAGENESIS OF ARG-40; LYS-41; ALA-95;
RP ILE-193 AND PHE-204, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP ACTIVITY REGULATION, REACTION MECHANISM, AND SUBSTRATE SPECIFICITY.
RX PubMed=18335995; DOI=10.1021/bi800023a;
RA Xu H., Sullivan T.J., Sekiguchi J., Kirikae T., Ojima I., Stratton C.F.,
RA Mao W., Rock F.L., Alley M.R., Johnson F., Walker S.G., Tonge P.J.;
RT "Mechanism and inhibition of saFabI, the enoyl reductase from
RT Staphylococcus aureus.";
RL Biochemistry 47:4228-4236(2008).
CC -!- FUNCTION: Catalyzes the reduction of a carbon-carbon double bond in an
CC enoyl moiety that is covalently linked to an acyl carrier protein
CC (ACP). It has a preference for a long chain (C12) substrate compared to
CC the shorter (C4) acyl group. Involved in the elongation cycle of fatty
CC acid which are used in the lipid metabolism (By similarity).
CC {ECO:0000250, ECO:0000269|PubMed:18335995}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2,3-saturated acyl-[ACP] + NADP(+) = a (2E)-enoyl-[ACP] +
CC H(+) + NADPH; Xref=Rhea:RHEA:22564, Rhea:RHEA-COMP:9925, Rhea:RHEA-
CC COMP:9926, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:78784, ChEBI:CHEBI:78785; EC=1.3.1.39;
CC Evidence={ECO:0000269|PubMed:18335995};
CC -!- ACTIVITY REGULATION: Inhibited by 1,4-disubstituted imidazoles, 1,4-
CC benzodiazepine, naphthyridinone derivatives, triclosan and its diphenyl
CC ether analgues. {ECO:0000269|PubMed:11514139,
CC ECO:0000269|PubMed:12109908, ECO:0000269|PubMed:12699381,
CC ECO:0000269|PubMed:18335995}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.5 uM for dodecenoyl ACP (DD-ACP)(with NADPH at 25 degrees
CC Celsius and pH 7.8) {ECO:0000269|PubMed:18335995};
CC KM=70.8 uM for NADPH (with DD-ACP at 25 degrees Celsius and pH 7.8)
CC {ECO:0000269|PubMed:18335995};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250}.
CC -!- MISCELLANEOUS: Follows a sequential ordered bi-bi catalytic mechanism.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. FabI subfamily. {ECO:0000305}.
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DR EMBL; CP000253; ABD30072.1; -; Genomic_DNA.
DR RefSeq; WP_000933197.1; NZ_LS483365.1.
DR RefSeq; YP_499500.1; NC_007795.1.
DR PDB; 6TBB; X-ray; 2.45 A; A/B/C/D/E/F/G/H=3-256.
DR PDB; 6TBC; X-ray; 2.55 A; A/B/C/D/E/F/G/H=3-256.
DR PDB; 6YUR; X-ray; 1.96 A; A/B/C/D/E/F/G/H=1-256.
DR PDBsum; 6TBB; -.
DR PDBsum; 6TBC; -.
DR PDBsum; 6YUR; -.
DR AlphaFoldDB; Q2FZQ3; -.
DR SMR; Q2FZQ3; -.
DR STRING; 1280.SAXN108_1007; -.
DR BindingDB; Q2FZQ3; -.
DR EnsemblBacteria; ABD30072; ABD30072; SAOUHSC_00947.
DR GeneID; 3920658; -.
DR KEGG; sao:SAOUHSC_00947; -.
DR PATRIC; fig|93061.5.peg.868; -.
DR eggNOG; COG0623; Bacteria.
DR HOGENOM; CLU_010194_10_1_9; -.
DR OMA; GILDMIH; -.
DR SABIO-RK; Q2FZQ3; -.
DR UniPathway; UPA00094; -.
DR PHI-base; PHI:7915; -.
DR Proteomes; UP000008816; Chromosome.
DR GO; GO:0004318; F:enoyl-[acyl-carrier-protein] reductase (NADH) activity; IDA:UniProtKB.
DR GO; GO:0047117; F:enoyl-[acyl-carrier-protein] reductase (NADPH, A-specific) activity; IEA:UniProtKB-EC.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0050661; F:NADP binding; IDA:UniProtKB.
DR GO; GO:0030497; P:fatty acid elongation; ISS:UniProtKB.
DR CDD; cd05372; ENR_SDR; 1.
DR InterPro; IPR014358; Enoyl-ACP_Rdtase_NADH.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR PANTHER; PTHR43159; PTHR43159; 1.
DR PIRSF; PIRSF000094; Enoyl-ACP_rdct; 1.
DR PRINTS; PR00081; GDHRDH.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Fatty acid biosynthesis; Fatty acid metabolism;
KW Lipid biosynthesis; Lipid metabolism; NAD; NADP; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..256
FT /note="Enoyl-[acyl-carrier-protein] reductase [NADPH] FabI"
FT /id="PRO_0000407978"
FT ACT_SITE 147
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 157
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 13
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 19..20
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 40..44
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 66..67
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 94
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 97
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 164
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 193..197
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT SITE 40
FT /note="Critical for cofactor specificity"
FT SITE 41
FT /note="Critical for cofactor specificity"
FT SITE 205
FT /note="Involved in acyl-ACP binding"
FT /evidence="ECO:0000250"
FT MUTAGEN 40
FT /note="R->Q: Exhibits an 50-fold decrease in kcat/ Km for
FT NADPH, whereas kcat/Km for NADH increases by 5-7-fold."
FT /evidence="ECO:0000269|PubMed:18335995"
FT MUTAGEN 41
FT /note="K->N: Exhibits an 50-fold decrease in kcat/ Km for
FT NADPH, whereas kcat/Km for NADH increases by 5-7-fold."
FT /evidence="ECO:0000269|PubMed:18335995"
FT MUTAGEN 95
FT /note="A->V: Exhibits an 240-fold decrease in kcat/ Km for
FT NADPH, whereas kcat/Km for DD-ACP decreases only by 18-
FT fold."
FT /evidence="ECO:0000269|PubMed:18335995"
FT MUTAGEN 193
FT /note="I->S: Exhibits an 13-fold decrease in kcat/ Km for
FT NADPH, whereas kcat/Km for DD-ACP decreases only by 6-
FT fold."
FT /evidence="ECO:0000269|PubMed:18335995"
FT MUTAGEN 204
FT /note="F->S: Exhibits an 10-fold decrease in kcat/ Km for
FT NADPH, whereas kcat/Km for DD-ACP decreases only by 4-
FT fold."
FT /evidence="ECO:0000269|PubMed:18335995"
FT STRAND 8..12
FT /evidence="ECO:0007829|PDB:6YUR"
FT HELIX 20..30
FT /evidence="ECO:0007829|PDB:6YUR"
FT STRAND 34..41
FT /evidence="ECO:0007829|PDB:6YUR"
FT HELIX 42..51
FT /evidence="ECO:0007829|PDB:6YUR"
FT TURN 52..54
FT /evidence="ECO:0007829|PDB:6YUR"
FT STRAND 62..64
FT /evidence="ECO:0007829|PDB:6YUR"
FT HELIX 70..84
FT /evidence="ECO:0007829|PDB:6YUR"
FT STRAND 88..92
FT /evidence="ECO:0007829|PDB:6YUR"
FT HELIX 99..101
FT /evidence="ECO:0007829|PDB:6YUR"
FT STRAND 102..104
FT /evidence="ECO:0007829|PDB:6YUR"
FT HELIX 106..108
FT /evidence="ECO:0007829|PDB:6YUR"
FT HELIX 111..121
FT /evidence="ECO:0007829|PDB:6YUR"
FT HELIX 123..133
FT /evidence="ECO:0007829|PDB:6YUR"
FT STRAND 140..146
FT /evidence="ECO:0007829|PDB:6YUR"
FT HELIX 148..150
FT /evidence="ECO:0007829|PDB:6YUR"
FT TURN 155..157
FT /evidence="ECO:0007829|PDB:6YUR"
FT HELIX 158..178
FT /evidence="ECO:0007829|PDB:6YUR"
FT HELIX 179..181
FT /evidence="ECO:0007829|PDB:6YUR"
FT STRAND 183..190
FT /evidence="ECO:0007829|PDB:6YUR"
FT HELIX 197..200
FT /evidence="ECO:0007829|PDB:6YUR"
FT HELIX 204..214
FT /evidence="ECO:0007829|PDB:6YUR"
FT HELIX 223..234
FT /evidence="ECO:0007829|PDB:6YUR"
FT HELIX 236..238
FT /evidence="ECO:0007829|PDB:6YUR"
FT STRAND 245..249
FT /evidence="ECO:0007829|PDB:6YUR"
FT HELIX 252..254
FT /evidence="ECO:0007829|PDB:6YUR"
SQ SEQUENCE 256 AA; 28022 MW; 6955A2FF5CD65A15 CRC64;
MLNLENKTYV IMGIANKRSI AFGVAKVLDQ LGAKLVFTYR KERSRKELEK LLEQLNQPEA
HLYQIDVQSD EEVINGFEQI GKDVGNIDGV YHSIAFANME DLRGRFSETS REGFLLAQDI
SSYSLTIVAH EAKKLMPEGG SIVATTYLGG EFAVQNYNVM GVAKASLEAN VKYLALDLGP
DNIRVNAISA SPIRTLSAKG VGGFNTILKE IEERAPLKRN VDQVEVGKTA AYLLSDLSSG
VTGENIHVDS GFHAIK
