アイテム詳細

要旨

F₄₂₀-dependent secondary alcohol dehydrogenase (Adf) from methanogenic archaea is a member of the growing bacterial luciferase family which are all TIM barrel enzymes, most of which with an unusual nonprolyl cis peptide bond. We report here on the crystal structure of Adf from Methanoculleus thermophilicus at 1.8 Å resolution in complex with a F₄₂₀-acetone adduct. The knowledge of the F₄₂₀ binding mode in Adf provides the molecular basis for modeling F₄₂₀ and FMN into the other enzymes of the family. A nonprolyl cis peptide bond was identified as an essential part of a bulge that serves as backstop at the Re-face of F₄₂₀ to keep it in a bent conformation. The acetone moiety of the F₄₂₀-acetone adduct is positioned at the Si-face of F₄₂₀ deeply buried inside the protein. Isopropanol can be reliably modeled and a hydrogen transfer mechanism postulated. His39 and Glu108 can be identified as key players for binding of the acetone or isopropanol oxygens and for catalysis.