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Protein

3-oxoacyl-[acyl-carrier-protein] reductase FabG1

Gene

fabG1

Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the NADPH-dependent reduction of beta-ketoacyl-ACP substrates to beta-hydroxyacyl-ACP products, the first reductive step in the elongation cycle of fatty acid biosynthesis. MabA preferentially metabolizes long-chain substrates (C8-C20) and has a poor affinity for the C4 substrate.3 Publications

Catalytic activityi

(3R)-3-hydroxyacyl-[acyl-carrier-protein] + NADP+ = 3-oxoacyl-[acyl-carrier-protein] + NADPH.1 Publication

Kineticsi

  1. KM=8.3 µM for beta-ketododecanoyl-CoA (at 25 degrees Celsius and at pH 7.0)1 Publication
  2. KM=41 µM for NADPH (at 25 degrees Celsius and at pH 7.0)1 Publication
  3. KM=70 µM for beta-ketooctanoyl-CoA (at 25 degrees Celsius and at pH 7.0)1 Publication
  4. KM=1530 µM for acetoacetyl-CoA (at 25 degrees Celsius and at pH 7.0)1 Publication

    Pathwayi: fatty acid biosynthesis

    This protein is involved in the pathway fatty acid biosynthesis, which is part of Lipid metabolism.
    View all proteins of this organism that are known to be involved in the pathway fatty acid biosynthesis and in Lipid metabolism.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei27 – 271NADP; via amide nitrogen
    Binding sitei47 – 471NADP
    Binding sitei88 – 881NADP; via amide nitrogen
    Binding sitei140 – 1401SubstrateBy similarity
    Active sitei153 – 1531Proton acceptorPROSITE-ProRule annotation
    Binding sitei186 – 1861NADP; via amide nitrogen and carbonyl oxygenBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi22 – 254NADP
    Nucleotide bindingi61 – 622NADP
    Nucleotide bindingi153 – 1575NADPBy similarity

    GO - Molecular functioni

    • 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity Source: MTBBASE
    • acetoacetyl-CoA reductase activity Source: MTBBASE

    GO - Biological processi

    • mycolic acid biosynthetic process Source: MTBBASE
    • oxidation-reduction process Source: MTBBASE
    • short-chain fatty acid metabolic process Source: MTBBASE
    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism

    Keywords - Ligandi

    NADP

    Enzyme and pathway databases

    UniPathwayiUPA00094.

    Chemistry

    SwissLipidsiSLP:000001159.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    3-oxoacyl-[acyl-carrier-protein] reductase FabG1 (EC:1.1.1.100)
    Alternative name(s):
    3-ketoacyl-acyl carrier protein reductase
    Beta-ketoacyl-ACP reductase
    Beta-ketoacyl-acyl carrier protein reductase
    Gene namesi
    Name:fabG1
    Synonyms:mabA
    Ordered Locus Names:Rv1483
    ORF Names:MTCY277.04
    OrganismiMycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
    Taxonomic identifieri83332 [NCBI]
    Taxonomic lineageiBacteriaActinobacteriaCorynebacterialesMycobacteriaceaeMycobacteriumMycobacterium tuberculosis complex
    Proteomesi
    • UP000001584 Componenti: Chromosome

    Organism-specific databases

    TubercuListiRv1483.

    Subcellular locationi

    GO - Cellular componenti

    • plasma membrane Source: MTBBASE
    Complete GO annotation...

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi60 – 601C → V: Displays a lower activity than the wild-type and a slightly decreased affinity for the cofactor. Totally inactive; when associated with A-139 and L-144. 2 Publications
    Mutagenesisi139 – 1391G → A: Complete protein inactivation and freezes the catalytic site into its closed form. Totally inactive; when associated with V-60 and L-144. 1 Publication
    Mutagenesisi144 – 1441S → L: Stabilizes the catalytic loop in its open active form. Totally inactive; when associated with V-60 and A-139. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methionineiRemovedCombined sources
    Chaini2 – 2472463-oxoacyl-[acyl-carrier-protein] reductase FabG1PRO_0000054677Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylthreonineCombined sources

    Keywords - PTMi

    Acetylation

    Proteomic databases

    PaxDbiP9WGT3.

    Interactioni

    Subunit structurei

    Homotetramer.3 Publications

    Protein-protein interaction databases

    STRINGi83332.Rv1483.

    Structurei

    Secondary structure

    1
    247
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi17 – 204Combined sources
    Turni21 – 244Combined sources
    Helixi26 – 3712Combined sources
    Beta strandi41 – 499Combined sources
    Beta strandi55 – 595Combined sources
    Helixi65 – 7915Combined sources
    Beta strandi83 – 886Combined sources
    Turni97 – 993Combined sources
    Helixi102 – 11211Combined sources
    Helixi114 – 12916Combined sources
    Beta strandi133 – 1386Combined sources
    Helixi142 – 1454Combined sources
    Helixi151 – 17121Combined sources
    Helixi172 – 1743Combined sources
    Beta strandi176 – 1838Combined sources
    Helixi189 – 1935Combined sources
    Helixi196 – 2027Combined sources
    Helixi203 – 2053Combined sources
    Helixi214 – 22512Combined sources
    Helixi227 – 2293Combined sources
    Beta strandi236 – 2405Combined sources
    Turni241 – 2444Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1UZLX-ray2.00A/B1-247[»]
    1UZMX-ray1.49A/B1-247[»]
    1UZNX-ray1.91A/B1-247[»]
    2NTNX-ray2.30A/B1-247[»]
    ProteinModelPortaliP9WGT3.
    SMRiP9WGT3. Positions 9-247.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiENOG4105CHR. Bacteria.
    ENOG410XNW1. LUCA.
    KOiK11610.
    OMAiRVKDEDW.
    PhylomeDBiP9WGT3.

    Family and domain databases

    Gene3Di3.40.50.720. 1 hit.
    InterProiIPR016040. NAD(P)-bd_dom.
    IPR020904. Sc_DH/Rdtase_CS.
    IPR002347. SDR_fam.
    [Graphical view]
    PANTHERiPTHR24322. PTHR24322. 2 hits.
    PRINTSiPR00081. GDHRDH.
    PR00080. SDRFAMILY.
    SUPFAMiSSF51735. SSF51735. 1 hit.
    PROSITEiPS00061. ADH_SHORT. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P9WGT3-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MTATATEGAK PPFVSRSVLV TGGNRGIGLA IAQRLAADGH KVAVTHRGSG
    60 70 80 90 100
    APKGLFGVEC DVTDSDAVDR AFTAVEEHQG PVEVLVSNAG LSADAFLMRM
    110 120 130 140 150
    TEEKFEKVIN ANLTGAFRVA QRASRSMQRN KFGRMIFIGS VSGSWGIGNQ
    160 170 180 190 200
    ANYAASKAGV IGMARSIARE LSKANVTANV VAPGYIDTDM TRALDERIQQ
    210 220 230 240
    GALQFIPAKR VGTPAEVAGV VSFLASEDAS YISGAVIPVD GGMGMGH
    Length:247
    Mass (Da):25,697
    Last modified:April 16, 2014 - v1
    Checksum:i70F6254B0FFFCD47
    GO

    Mass spectrometryi

    Molecular mass is 27729 Da from positions 2 - 247. Determined by ESI. Recombinant protein expressed in E.coli.1 Publication

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U66801 Genomic DNA. Translation: AAC69639.1.
    AL123456 Genomic DNA. Translation: CCP44243.1.
    PIRiF70710.
    RefSeqiNP_215999.1. NC_000962.3.
    WP_003898892.1. NZ_KK339370.1.

    Genome annotation databases

    EnsemblBacteriaiCCP44243; CCP44243; Rv1483.
    GeneIDi886551.
    KEGGimtu:Rv1483.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U66801 Genomic DNA. Translation: AAC69639.1.
    AL123456 Genomic DNA. Translation: CCP44243.1.
    PIRiF70710.
    RefSeqiNP_215999.1. NC_000962.3.
    WP_003898892.1. NZ_KK339370.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1UZLX-ray2.00A/B1-247[»]
    1UZMX-ray1.49A/B1-247[»]
    1UZNX-ray1.91A/B1-247[»]
    2NTNX-ray2.30A/B1-247[»]
    ProteinModelPortaliP9WGT3.
    SMRiP9WGT3. Positions 9-247.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi83332.Rv1483.

    Chemistry

    SwissLipidsiSLP:000001159.

    Proteomic databases

    PaxDbiP9WGT3.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiCCP44243; CCP44243; Rv1483.
    GeneIDi886551.
    KEGGimtu:Rv1483.

    Organism-specific databases

    TubercuListiRv1483.

    Phylogenomic databases

    eggNOGiENOG4105CHR. Bacteria.
    ENOG410XNW1. LUCA.
    KOiK11610.
    OMAiRVKDEDW.
    PhylomeDBiP9WGT3.

    Enzyme and pathway databases

    UniPathwayiUPA00094.

    Family and domain databases

    Gene3Di3.40.50.720. 1 hit.
    InterProiIPR016040. NAD(P)-bd_dom.
    IPR020904. Sc_DH/Rdtase_CS.
    IPR002347. SDR_fam.
    [Graphical view]
    PANTHERiPTHR24322. PTHR24322. 2 hits.
    PRINTSiPR00081. GDHRDH.
    PR00080. SDRFAMILY.
    SUPFAMiSSF51735. SSF51735. 1 hit.
    PROSITEiPS00061. ADH_SHORT. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "The mabA gene from the inhA operon of Mycobacterium tuberculosis encodes a 3-ketoacyl reductase that fails to confer isoniazid resistance."
      Banerjee A., Sugantino M., Sacchettini J.C., Jacobs W.R. Jr.
      Microbiology 144:2697-2704(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION AS A BETA-KETOACYL-ACP REDUCTASE.
      Strain: ATCC 25618 / H37Rv.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: ATCC 25618 / H37Rv.
    3. "MabA (FabG1), a Mycobacterium tuberculosis protein involved in the long-chain fatty acid elongation system FAS-II."
      Marrakchi H., Ducasse S., Labesse G., Montrozier H., Margeat E., Emorine L., Charpentier X., Daffe M., Quemard A.
      Microbiology 148:951-960(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN FATTY ACID BIOSYNTHESIS, CATALYTIC ACTIVITY, MASS SPECTROMETRY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT.
    4. "The essential mycobacterial genes, fabG1 and fabG4, encode 3-oxoacyl-thioester reductases that are functional in yeast mitochondrial fatty acid synthase type 2."
      Gurvitz A.
      Mol. Genet. Genomics 282:407-416(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS A BETA-KETOACYL-ACP REDUCTASE, SUBSTRATE SPECIFICITY.
    5. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS], IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Strain: ATCC 25618 / H37Rv.
    6. "Crystal structure of MabA from Mycobacterium tuberculosis, a reductase involved in long-chain fatty acid biosynthesis."
      Cohen-Gonsaud M., Ducasse S., Hoh F., Zerbib D., Labesse G., Quemard A.
      J. Mol. Biol. 320:249-261(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF MUTANT CYS-60 AND WILD-TYPE, MUTAGENESIS OF CYS-60, SUBUNIT, NOMENCLATURE.
    7. "Lack of dynamics in the MabA active site kills the enzyme activity: practical consequences for drug-design studies."
      Poncet-Montange G., Ducasse-Cabanot S., Quemard A., Labesse G., Cohen-Gonsaud M.
      Acta Crystallogr. D 63:923-925(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF MUTANT VAL-60/ALA-139/LEU-144, MUTAGENESIS OF CYS-60; GLY-139 AND SER-144, SUBUNIT.

    Entry informationi

    Entry nameiFABG_MYCTU
    AccessioniPrimary (citable) accession number: P9WGT3
    Secondary accession number(s): L0T9R6
    , P0A5Y4, P71764, Q48930
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 16, 2014
    Last sequence update: April 16, 2014
    Last modified: May 11, 2016
    This is version 20 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh
      Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh: entries and gene names
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.