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Protein

3alpha-hydroxy bile acid-CoA-ester 3-dehydrogenase 2

Gene

baiA2

Organism
Clostridium scindens (strain JCM 10418 / VPI 12708)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in the multi-step bile acid 7alpha-dehydroxylation pathway that transforms primary bile acids to secondary bile acids in the human gut (PubMed:23836456, PubMed:16299351). Catalyzes the oxidation of C3-hydroxyl group of CoA conjugated bile acids generating a C3-oxo bile acid intermediate. Can use choloyl-CoA, chenodeoxycholoyl-CoA, deoxycholoyl-CoA, and lithocholoyl-CoA as substrates with similar efficiency. Highly prefers NAD over NADP as cosubstrate. Also catalyzes the reverse reactions; in vitro, the preferred direction of reaction depends on the pH. Has very little activity with unconjugated (non-CoA) bile acid substrates (PubMed:23836456).1 Publication1 Publication

Miscellaneous

There are three genes for BaiA proteins: baiA1 is identical to baiA3 and encodes a polypeptide sharing 92% identity with baiA2 gene product.Curated
Reaction mechanism seems to proceed via a nicotinamide-OH- adduct, which is proposed to be involved in proton relay instead of hydride transfer.1 Publication

Catalytic activityi

A 3-alpha-hydroxy bile acid CoA ester + NAD+ = a 3-oxo bile acid CoA ester + NADH.1 Publication
Choloyl-CoA + NAD+ = 3-oxocholoyl-CoA + NADH.1 Publication
Chenodeoxycholoyl-CoA + NAD+ = 3-oxochenodeoxycholoyl-CoA + NADH.1 Publication
Deoxycholoyl-CoA + NAD+ = 3-oxodeoxycholoyl-CoA + NADH.1 Publication
Lithocholoyl-CoA + NAD+ = 3-oxolithocholoyl-CoA + NADH.1 Publication

Kineticsi

kcat is 10 min(-1) with choloyl-CoA as substrate. kcat is 12 min(-1) with chenodeoxycholoyl-CoA as substrate. kcat is 11 min(-1) with lithocholoyl-CoA as substrate. kcat is 9.5 min(-1) with deoxycholoyl-CoA as substrate. kcat is 8.3 min(-1) with 3-oxocholoyl-CoA as substrate. kcat is 10 min(-1) with 3-oxochenodeoxycholoyl-CoA as substrate. kcat is 7.3 min(-1) with 3-oxolithocholoyl-CoA as substrate. kcat is 9.1 min(-1) with 3-oxodeoxycholoyl-CoA as substrate (at pH 8.7 and 37 degrees Celsius).1 Publication
  1. KM=32 µM for choloyl-CoA (at pH 8.7 and 37 degrees Celsius)1 Publication
  2. KM=23 µM for chenodeoxycholoyl-CoA (at pH 8.7 and 37 degrees Celsius)1 Publication
  3. KM=18 µM for lithocholoyl-CoA (at pH 8.7 and 37 degrees Celsius)1 Publication
  4. KM=17 µM for deoxycholoyl-CoA (at pH 8.7 and 37 degrees Celsius)1 Publication
  5. KM=1.8 µM for 3-oxocholoyl-CoA (at pH 8.7 and 37 degrees Celsius)1 Publication
  6. KM=1.1 µM for 3-oxochenodeoxycholoyl-CoA (at pH 8.7 and 37 degrees Celsius)1 Publication
  7. KM=1.3 µM for 3-oxolithocholoyl-CoA (at pH 8.7 and 37 degrees Celsius)1 Publication
  8. KM=1.5 µM for 3-oxodeoxycholoyl-CoA (at pH 8.7 and 37 degrees Celsius)1 Publication
  9. KM=6.7 µM for NAD+ (at pH 8.7 and 37 degrees Celsius)1 Publication
  10. KM=84 µM for NADP+ (at pH 8.7 and 37 degrees Celsius)1 Publication

    pH dependencei

    The direction of reaction is pH dependent in vitro. At pH 7.3, clearly the reduction reaction is preferred with an order of magnitude higher velocity than the oxidation reaction. At pH 8.7, the velocities of the oxidation and reduction reaction are comparable. At pH 9.9 the velocity of the reduction reaction is about 60% of oxidation reaction.1 Publication

    Pathwayi: bile acid biosynthesis

    This protein is involved in the pathway bile acid biosynthesis, which is part of Lipid metabolism.1 Publication1 Publication
    View all proteins of this organism that are known to be involved in the pathway bile acid biosynthesis and in Lipid metabolism.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei38NAD; via amide nitrogenCombined sources1 Publication1
    Binding sitei42NADCombined sources1 Publication1
    Binding sitei92NAD; via carbonyl oxygenCombined sources1 Publication1
    Binding sitei144SubstrateBy similarity1
    Active sitei157Proton donor/acceptorPROSITE-ProRule annotation1 Publication1
    Active sitei161Proton donor/acceptor1 Publication1
    Binding sitei161NADCombined sources1 Publication1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi15 – 18NADCombined sources1 Publication4
    Nucleotide bindingi190 – 192NADCombined sources1 Publication3

    GO - Molecular functioni

    • bile acid binding Source: UniProtKB
    • NAD+ binding Source: UniProtKB
    • steroid dehydrogenase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor Source: UniProtKB

    GO - Biological processi

    • bile acid biosynthetic process Source: UniProtKB-UniPathway
    • bile acid metabolic process Source: UniProtKB
    • protein homotetramerization Source: UniProtKB
    • response to bile acid Source: UniProtKB

    Keywordsi

    Molecular functionOxidoreductase
    Biological processLipid metabolism, Steroid metabolism
    LigandNAD

    Enzyme and pathway databases

    BioCyciMetaCyc:BAIA2EUBSP-MONOMER.
    UniPathwayiUPA00221.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    3alpha-hydroxy bile acid-CoA-ester 3-dehydrogenase 21 Publication (EC:1.1.1.3951 Publication)
    Alternative name(s):
    3alpha-hydroxysteroid dehydrogenase 22 Publications
    Short name:
    3alpha-HSDH 21 Publication
    Bile acid-inducible protein BaiA21 Publication
    Gene namesi
    Name:baiA2
    OrganismiClostridium scindens (strain JCM 10418 / VPI 12708)
    Taxonomic identifieri29347 [NCBI]
    Taxonomic lineageiBacteriaFirmicutesClostridiaClostridialesLachnospiraceae

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi42E → A: Improves utilization of NADP(+) as cosubstrate by 10-fold compared to wild-type. Displays 6-fold increase in affinity for NADP(+). 1 Publication1

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000545251 – 2493alpha-hydroxy bile acid-CoA-ester 3-dehydrogenase 2Add BLAST249

    Expressioni

    Inductioni

    Induced by the C24 primary bile acids cholic acid (CA) and chenodeoxycholic acid (CDCA).1 Publication

    Interactioni

    Subunit structurei

    Homotetramer.1 Publication

    Protein-protein interaction databases

    STRINGi411468.CLOSCI_03133.

    Structurei

    Secondary structure

    1249
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Turni3 – 6Combined sources4
    Beta strandi8 – 11Combined sources4
    Turni12 – 15Combined sources4
    Helixi17 – 28Combined sources12
    Beta strandi32 – 36Combined sources5
    Helixi40 – 53Combined sources14
    Beta strandi60 – 62Combined sources3
    Helixi69 – 83Combined sources15
    Beta strandi88 – 91Combined sources4
    Helixi101 – 103Combined sources3
    Helixi106 – 116Combined sources11
    Helixi118 – 131Combined sources14
    Turni132 – 135Combined sources4
    Beta strandi137 – 142Combined sources6
    Helixi146 – 149Combined sources4
    Helixi160 – 174Combined sources15
    Helixi176 – 178Combined sources3
    Beta strandi180 – 187Combined sources8
    Helixi193 – 196Combined sources4
    Helixi200 – 209Combined sources10
    Helixi218 – 229Combined sources12
    Helixi231 – 233Combined sources3
    Beta strandi238 – 243Combined sources6

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    4IS2X-ray1.90A1-249[»]
    4IS3X-ray2.00A/B/C/D1-249[»]
    ProteinModelPortaliP19337.
    SMRiP19337.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiENOG4105CHR. Bacteria.
    ENOG410XNW1. LUCA.

    Family and domain databases

    InterProiView protein in InterPro
    IPR016040. NAD(P)-bd_dom.
    IPR020904. Sc_DH/Rdtase_CS.
    IPR002347. SDR_fam.
    PfamiView protein in Pfam
    PF00106. adh_short. 1 hit.
    PRINTSiPR00081. GDHRDH.
    PR00080. SDRFAMILY.
    SUPFAMiSSF51735. SSF51735. 1 hit.
    PROSITEiView protein in PROSITE
    PS00061. ADH_SHORT. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    P19337-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MNLVQDKVTI ITGGTRGIGF AAAKIFIDNG AKVSIFGETQ EEVDTALAQL
    60 70 80 90 100
    KELYPEEEVL GFAPDLTSRD AVMAAVGQVA QKYGRLDVMI NNAGITSNNV
    110 120 130 140 150
    FSRVSEEEFK HIMDINVTGV FNGAWCAYQC MKDAKKGVII NTASVTGIFG
    160 170 180 190 200
    SLSGVGYPAS KASVIGLTHG LGREIIRKNI RVVGVAPGVV NTDMTNGNPP
    210 220 230 240
    EIMEGYLKAL PMKRMLEPEE IANVYLFLAS DLASGITATT VSVDGAYRP
    Length:249
    Mass (Da):26,538
    Last modified:November 1, 1990 - v1
    Checksum:i9A39B78BB63DC5AF
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M22623 Genomic DNA. Translation: AAB61150.1.
    U57489 Genomic DNA. Translation: AAC45414.1.
    PIRiA31841.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M22623 Genomic DNA. Translation: AAB61150.1.
    U57489 Genomic DNA. Translation: AAC45414.1.
    PIRiA31841.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    4IS2X-ray1.90A1-249[»]
    4IS3X-ray2.00A/B/C/D1-249[»]
    ProteinModelPortaliP19337.
    SMRiP19337.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi411468.CLOSCI_03133.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Phylogenomic databases

    eggNOGiENOG4105CHR. Bacteria.
    ENOG410XNW1. LUCA.

    Enzyme and pathway databases

    UniPathwayiUPA00221.
    BioCyciMetaCyc:BAIA2EUBSP-MONOMER.

    Family and domain databases

    InterProiView protein in InterPro
    IPR016040. NAD(P)-bd_dom.
    IPR020904. Sc_DH/Rdtase_CS.
    IPR002347. SDR_fam.
    PfamiView protein in Pfam
    PF00106. adh_short. 1 hit.
    PRINTSiPR00081. GDHRDH.
    PR00080. SDRFAMILY.
    SUPFAMiSSF51735. SSF51735. 1 hit.
    PROSITEiView protein in PROSITE
    PS00061. ADH_SHORT. 1 hit.
    ProtoNetiSearch...

    Entry informationi

    Entry nameiBAIA2_CLOSV
    AccessioniPrimary (citable) accession number: P19337
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1990
    Last sequence update: November 1, 1990
    Last modified: May 10, 2017
    This is version 101 of the entry and version 1 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. 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.