6BQE

Low-resolution structure of cyclohexadienyl dehydratase from Pseudomonas aeruginosa in space group P4322.

Replaces:  5JOT

Summary for 6BQE

• Entry DOI: 10.2210/pdb6bqe/pdb
• Descriptor: Arogenate dehydratase, ACETATE ION (3 entities in total)
• Functional Keywords: lyase, phenylalanine biosynthesis, cyclohexadienyl dehydratase, periplasmic binding protein
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 3
• Total formula weight: 88225.07

Authors

Clifton, B.E.,Carr, P.D.,Jackson, C.J. (deposition date: 2017-11-27, release date: 2017-12-13, Last modification date: 2024-10-30)

Primary citation

Clifton, B.E.,Kaczmarski, J.A.,Carr, P.D.,Gerth, M.L.,Tokuriki, N.,Jackson, C.J.
Evolution of cyclohexadienyl dehydratase from an ancestral solute-binding protein.
Nat. Chem. Biol., 14:542-547, 2018

PubMed Abstract: The emergence of enzymes through the neofunctionalization of noncatalytic proteins is ultimately responsible for the extraordinary range of biological catalysts observed in nature. Although the evolution of some enzymes from binding proteins can be inferred by homology, we have a limited understanding of the nature of the biochemical and biophysical adaptations along these evolutionary trajectories and the sequence in which they occurred. Here we reconstructed and characterized evolutionary intermediate states linking an ancestral solute-binding protein to the extant enzyme cyclohexadienyl dehydratase. We show how the intrinsic reactivity of a desolvated general acid was harnessed by a series of mutations radiating from the active site, which optimized enzyme-substrate complementarity and transition-state stabilization and minimized sampling of noncatalytic conformations. Our work reveals the molecular evolutionary processes that underlie the emergence of enzymes de novo, which are notably mirrored by recent examples of computational enzyme design and directed evolution.

PubMed: 29686357
DOI: 10.1038/s41589-018-0043-2

Experimental method

X-RAY DIFFRACTION (3.2 Å)