Structure and functional characterization of a bile acid 7α dehydratase BaiE in secondary bile acid synthesis

Shiva Bhowmik, Hsien Po Chiu, David H. Jones, Hsiu Ju Chiu, Mitchell D. Miller, Qingping Xu, Carol L. Farr, Jason M. Ridlon, James E. Wells, Marc André Elsliger, Ian A. Wilson, Phillip B. Hylemon, Scott A. Lesley

Research output: Contribution to journalArticlepeer-review


Conversion of the primary bile acids cholic acid (CA) and chenodeoxycholic acid (CDCA) to the secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA) is performed by a few species of intestinal bacteria in the genus Clostridium through a multistep biochemical pathway that removes a 7α-hydroxyl group. The rate-determining enzyme in this pathway is bile acid 7α-dehydratase (baiE). In this study, crystal structures of apo-BaiE and its putative product-bound [3-oxo-Δ4,6-lithocholyl-Coenzyme A (CoA)] complex are reported. BaiE is a trimer with a twisted α+β barrel fold with similarity to the Nuclear Transport Factor 2 (NTF2) superfamily. Tyr30, Asp35, and His83 form a catalytic triad that is conserved across this family. Site-directed mutagenesis of BaiE from Clostridium scindens VPI 12708 confirm that these residues are essential for catalysis and also the importance of other conserved residues, Tyr54 and Arg146, which are involved in substrate binding and affect catalytic turnover. Steady-state kinetic studies reveal that the BaiE homologs are able to turn over 3-oxo-Δ4-bile acid and CoA-conjugated 3-oxo-Δ4-bile acid substrates with comparable efficiency questioning the role of CoA-conjugation in the bile acid metabolism pathway. Proteins 2016; 84:316-331.

Original languageEnglish (US)
Pages (from-to)316-331
Number of pages16
JournalProteins: Structure, Function and Bioinformatics
Issue number3
StatePublished - Mar 1 2016
Externally publishedYes


  • 7α-dehyroxylation
  • Bile acid 7α-dehydratase
  • Gut microbe mediated human metabolite
  • Gut microbes
  • Nuclear transport factor-2 superfamily
  • Primary bile acid
  • Secondary bile acid
  • Secondary bile acid synthesis
  • Structural genomics

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology


Dive into the research topics of 'Structure and functional characterization of a bile acid 7α dehydratase BaiE in secondary bile acid synthesis'. Together they form a unique fingerprint.

Cite this