Structural Insight into Substrate Specificity of 3-Hydroxypropionyl-Coenzyme A Dehydratase from Metallosphaera sedula

Sci Rep. 2018 Jul 16;8(1):10692. doi: 10.1038/s41598-018-29070-w.


Metallosphaera sedula is a thermoacidophilic autotrophic archaeon known to utilize the 3-hydroxypropionate/4-hydroxybutyrate cycle (3-HP/4-HB cycle) as carbon fixation pathway. 3-Hydroxypropionyl-CoA dehydratase (3HPCD) is an enzyme involved in the 3-HP/4-HB cycle by converting 3-hydroxypropionyl-CoA to acryloyl-CoA. To elucidate the molecular mechanism of 3HPCD from M. sedula (Ms3HPCD), we determined its crystal structure in complex with Coenzyme A (CoA). Ms3HPCD showed an overall structure and the CoA-binding mode similar to other enoyl-CoA hydratase (ECH) family enzymes. However, compared with the other ECHs, Ms3HPCD has a tightly formed α3 helix near the active site, and bulky aromatic residues are located at the enoyl-group binding site, resulting in the enzyme having an optimal substrate binding site for accepting short-chain 3-hydroxyacyl-CoA as a substrate. Moreover, based on the phylogenetic tree analysis, we propose that the 3HPCD homologues from the phylum Crenarchaeota have an enoyl-group binding pocket similar to that of bacterial short-chain ECHs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Archaeal Proteins / chemistry
  • Archaeal Proteins / metabolism
  • Archaeal Proteins / ultrastructure*
  • Carbon Cycle*
  • Coenzyme A / metabolism
  • Coenzyme A / ultrastructure
  • Crystallography, X-Ray
  • Hydro-Lyases / genetics
  • Hydro-Lyases / metabolism
  • Hydro-Lyases / ultrastructure*
  • Hydroxybutyrates / metabolism
  • Lactic Acid / analogs & derivatives
  • Lactic Acid / metabolism
  • Molecular Docking Simulation
  • Phylogeny
  • Protein Structure, Quaternary
  • Substrate Specificity
  • Sulfolobaceae / enzymology*
  • Sulfolobaceae / genetics


  • Archaeal Proteins
  • Hydroxybutyrates
  • Lactic Acid
  • hydracrylic acid
  • Hydro-Lyases
  • Coenzyme A