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Protein

3-ketosteroid-9-alpha-monooxygenase, oxygenase component

Gene

kshA

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

Functioni

Involved in the degradation of cholesterol. Catalyzes the introduction of a 9a-hydroxyl moiety into 1,4-androstadiene-3,17-dione (ADD) to yield the 9alpha-hydroxy-1,4-androstadiene-3,17-dione (9OHADD) intermediate which spontaneously form 3-hydroxy-9,10-seconandrost-1,3,5(10)-triene-9,17-dione (HSA) via the meta-cleavage of ring B with concomitant aromatization of ring A. KSH is also able to use 4-androstene-3,17-dione (AD), 3-oxo-23,24-bisnorcholesta-4-en-22-oate (4-BNC), 3-oxo-23,24-bisnorcholesta-1,4-dien-22-oate (1,4-BNC), 3-oxo-23,24-bisnorcholesta-4-en-22-oyl-coenzyme A thioester (4-BNC-CoA) and 3-oxo-23,24-bisnorcholesta-1,4-dien-22-oyl-coenzyme A thioester (1,4-BNC-CoA) as substrates.2 Publications

Catalytic activityi

Androsta-1,4-diene-3,17-dione + NADH + O2 = 9-alpha-hydroxyandrosta-1,4-diene-3,17-dione + NAD+ + H2O.2 Publications

Cofactori

Protein has several cofactor binding sites:
  • [2Fe-2S] clusterPROSITE-ProRule annotation2 PublicationsNote: Binds 1 [2Fe-2S] cluster per subunit.PROSITE-ProRule annotation2 Publications
  • Fe cation2 PublicationsNote: Binds 1 Fe cation.2 Publications

Kineticsi

Kcat is 2.7 sec(-1) for 1,4-BNC-CoA as substrate (at pH 7 and at 22 degrees Celsius) (PubMed:21987574). Kcat is 0.8 sec(-1) for ADD as substrate (at pH 7 and at 25 degrees Celsius) (PubMed:19234303). Kcat is 0.61 sec(-1) for 4-BNC-CoA as substrate (at pH 7 and at 22 degrees Celsius) (PubMed:21987574). Kcat is 0.25 sec(-1) for 1,4-BNC as substrate (at pH 7 and at 22 degrees Celsius) (PubMed:21987574). Kcat is 0.08 sec(-1) for 4-BNC as substrate (at pH 7 and at 22 degrees Celsius) (PubMed:21987574). Kcat is 0.07 sec(-1) for AD as substrate (at pH 7 and at 25 degrees Celsius) (PubMed:19234303).2 Publications

Manual assertion based on experiment ini

  1. KM=3 µM for 4-BNC (at pH 7 and at 22 degrees Celsius)1 Publication
  2. KM=6.8 µM for 4-BNC-CoA (at pH 7 and at 22 degrees Celsius)1 Publication
  3. KM=17 µM for 1,4-BNC-CoA (at pH 7 and at 22 degrees Celsius)1 Publication
  4. KM=24 µM for AD (at pH 7 and at 25 degrees Celsius)1 Publication
  5. KM=70 µM for 1,4-BNC (at pH 7 and at 22 degrees Celsius)1 Publication
  6. KM=110 µM for ADD (at pH 7 and at 25 degrees Celsius)1 Publication

    Pathwayi: steroid biosynthesis

    This protein is involved in the pathway steroid biosynthesis, which is part of Lipid metabolism.1 Publication
    View all proteins of this organism that are known to be involved in the pathway steroid biosynthesis and in Lipid metabolism.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi67Iron-sulfur (2Fe-2S)PROSITE-ProRule annotation2 Publications1
    Metal bindingi69Iron-sulfur (2Fe-2S); via pros nitrogenPROSITE-ProRule annotation2 Publications1
    Metal bindingi86Iron-sulfur (2Fe-2S)PROSITE-ProRule annotation2 Publications1
    Metal bindingi89Iron-sulfur (2Fe-2S); via pros nitrogenPROSITE-ProRule annotation2 Publications1
    Metal bindingi175IronBy similarity1
    Metal bindingi181Iron; via tele nitrogen2 Publications1
    Metal bindingi186Iron; via tele nitrogen2 Publications1
    Metal bindingi304Iron2 Publications1

    GO - Molecular functioni

    • 2 iron, 2 sulfur cluster binding Source: UniProtKB
    • 3-ketosteroid 9-alpha-monooxygenase activity Source: UniProtKB-EC
    • ferrous iron binding Source: UniProtKB
    • iron ion binding Source: MTBBASE
    • ketosteroid monooxygenase activity Source: MTBBASE
    • steroid 9-alpha-monooxygenase activity Source: UniProtKB

    GO - Biological processi

    • cholesterol catabolic process Source: MTBBASE
    • pathogenesis Source: MTBBASE
    • protein homotrimerization Source: MTBBASE
    • response to cholesterol Source: MTBBASE
    • steroid biosynthetic process Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Cholesterol metabolism, Lipid degradation, Lipid metabolism, Steroid metabolism, Sterol metabolism, Virulence

    Keywords - Ligandi

    2Fe-2S, Iron, Iron-sulfur, Metal-binding, NAD

    Enzyme and pathway databases

    BioCyciMetaCyc:G185E-7803-MONOMER.
    MTBH37RV:G185E-7803-MONOMER.
    BRENDAi1.14.13.142. 3445.
    UniPathwayiUPA00062.

    Chemistry databases

    SwissLipidsiSLP:000001163.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    3-ketosteroid-9-alpha-monooxygenase, oxygenase component1 Publication
    Alternative name(s):
    3-ketosteroid-9-alpha-hydroxylase, oxygenase component1 Publication
    Short name:
    KSH1 Publication
    Androsta-1,4-diene-3,17-dione 9-alpha-hydroxylase1 Publication (EC:1.14.13.1422 Publications)
    Rieske-type oxygenase1 Publication
    Short name:
    RO1 Publication
    Gene namesi
    Name:kshA
    Ordered Locus Names:Rv3526
    OrganismiMycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
    Taxonomic identifieri83332 [NCBI]
    Taxonomic lineageiBacteriaActinobacteriaCorynebacterialesMycobacteriaceaeMycobacteriumMycobacterium tuberculosis complex
    Proteomesi
    • UP000001584 Componenti: Chromosome

    Organism-specific databases

    TubercuListiRv3526.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00004040981 – 3863-ketosteroid-9-alpha-monooxygenase, oxygenase componentAdd BLAST386

    Proteomic databases

    PaxDbiP71875.

    Expressioni

    Inductioni

    Induced by KstR.1 Publication

    Interactioni

    Subunit structurei

    Homotrimer (PubMed:19234303). The two-component system 3-ketosteroid-9-alpha-monooxygenase is composed of an oxygenase component KshA and a reductase component KshB (PubMed:21987574).2 Publications

    Protein-protein interaction databases

    STRINGi83332.Rv3526.

    Structurei

    Secondary structure

    1386
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi24 – 31Combined sources8
    Helixi32 – 35Combined sources4
    Beta strandi37 – 39Combined sources3
    Beta strandi41 – 45Combined sources5
    Beta strandi48 – 54Combined sources7
    Beta strandi60 – 66Combined sources7
    Turni68 – 70Combined sources3
    Helixi74 – 76Combined sources3
    Beta strandi77 – 80Combined sources4
    Beta strandi83 – 85Combined sources3
    Turni87 – 89Combined sources3
    Beta strandi92 – 94Combined sources3
    Beta strandi97 – 101Combined sources5
    Beta strandi119 – 122Combined sources4
    Beta strandi125 – 130Combined sources6
    Helixi139 – 141Combined sources3
    Helixi147 – 150Combined sources4
    Beta strandi158 – 167Combined sources10
    Helixi169 – 177Combined sources9
    Helixi181 – 184Combined sources4
    Beta strandi188 – 198Combined sources11
    Beta strandi201 – 210Combined sources10
    Beta strandi214 – 216Combined sources3
    Beta strandi219 – 221Combined sources3
    Beta strandi224 – 246Combined sources23
    Beta strandi249 – 263Combined sources15
    Beta strandi266 – 276Combined sources11
    Beta strandi279 – 281Combined sources3
    Helixi287 – 308Combined sources22
    Helixi321 – 323Combined sources3
    Helixi326 – 334Combined sources9
    Helixi335 – 337Combined sources3
    Helixi340 – 342Combined sources3
    Helixi345 – 348Combined sources4
    Beta strandi351 – 354Combined sources4
    Helixi358 – 372Combined sources15

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2ZYLX-ray2.30A1-386[»]
    4QCKX-ray2.46A1-386[»]
    ProteinModelPortaliP71875.
    SMRiP71875.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP71875.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini26 – 128RieskePROSITE-ProRule annotationAdd BLAST103

    Sequence similaritiesi

    Contains 1 Rieske domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiENOG4105CIJ. Bacteria.
    COG4638. LUCA.
    HOGENOMiHOG000052102.
    InParanoidiP71875.
    KOiK15982.
    OMAiAVYQMRR.
    PhylomeDBiP71875.

    Family and domain databases

    Gene3Di2.102.10.10. 1 hit.
    InterProiIPR017941. Rieske_2Fe-2S.
    [Graphical view]
    PfamiPF00355. Rieske. 1 hit.
    [Graphical view]
    SUPFAMiSSF50022. SSF50022. 1 hit.
    PROSITEiPS51296. RIESKE. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P71875-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MSTDTSGVGV REIDAGALPT RYARGWHCLG VAKDYLEGKP HGVEAFGTKL
    60 70 80 90 100
    VVFADSHGDL KVLDGYCRHM GGDLSEGTVK GDEVACPFHD WRWGGDGRCK
    110 120 130 140 150
    LVPYARRTPR MARTRSWTTD VRSGLLFVWH DHEGNPPDPA VRIPEIPEAA
    160 170 180 190 200
    SDEWTDWRWN RILIEGSNCR DIIDNVTDMA HFFYIHFGLP TYFKNVFEGH
    210 220 230 240 250
    IASQYLHNVG RPDVDDLGTS YGEAHLDSEA SYFGPSFMIN WLHNRYGNYK
    260 270 280 290 300
    SESILINCHY PVTQNSFVLQ WGVIVEKPKG MSEEMTDKLS RVFTEGVSKG
    310 320 330 340 350
    FLQDVEIWKH KTRIDNPLLV EEDGAVYQLR RWYEQFYVDV ADIKPEMVER
    360 370 380
    FEIEVDTKRA NEFWNAEVEK NLKSREVSDD VPAEQH
    Length:386
    Mass (Da):44,268
    Last modified:July 1, 1997 - v2
    Checksum:i510F89D334D230B4
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AL123456 Genomic DNA. Translation: CCP46348.1.
    PIRiG70674.
    RefSeqiNP_218043.1. NC_000962.3.
    WP_003419211.1. NZ_KK339374.1.

    Genome annotation databases

    EnsemblBacteriaiCCP46348; CCP46348; Rv3526.
    GeneIDi888268.
    KEGGimtu:Rv3526.
    PATRICi18156454. VBIMycTub87468_3937.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AL123456 Genomic DNA. Translation: CCP46348.1.
    PIRiG70674.
    RefSeqiNP_218043.1. NC_000962.3.
    WP_003419211.1. NZ_KK339374.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2ZYLX-ray2.30A1-386[»]
    4QCKX-ray2.46A1-386[»]
    ProteinModelPortaliP71875.
    SMRiP71875.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi83332.Rv3526.

    Chemistry databases

    SwissLipidsiSLP:000001163.

    Proteomic databases

    PaxDbiP71875.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiCCP46348; CCP46348; Rv3526.
    GeneIDi888268.
    KEGGimtu:Rv3526.
    PATRICi18156454. VBIMycTub87468_3937.

    Organism-specific databases

    TubercuListiRv3526.

    Phylogenomic databases

    eggNOGiENOG4105CIJ. Bacteria.
    COG4638. LUCA.
    HOGENOMiHOG000052102.
    InParanoidiP71875.
    KOiK15982.
    OMAiAVYQMRR.
    PhylomeDBiP71875.

    Enzyme and pathway databases

    UniPathwayiUPA00062.
    BioCyciMetaCyc:G185E-7803-MONOMER.
    MTBH37RV:G185E-7803-MONOMER.
    BRENDAi1.14.13.142. 3445.

    Miscellaneous databases

    EvolutionaryTraceiP71875.

    Family and domain databases

    Gene3Di2.102.10.10. 1 hit.
    InterProiIPR017941. Rieske_2Fe-2S.
    [Graphical view]
    PfamiPF00355. Rieske. 1 hit.
    [Graphical view]
    SUPFAMiSSF50022. SSF50022. 1 hit.
    PROSITEiPS51296. RIESKE. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiKSHA_MYCTU
    AccessioniPrimary (citable) accession number: P71875
    Secondary accession number(s): L0TCS9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 8, 2011
    Last sequence update: July 1, 1997
    Last modified: November 30, 2016
    This is version 108 of the entry and version 2 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.