title: Structure of a de novo designed protein model of radical enzymes.
abstract: The use of side chains as catalytic cofactors for protein mediated redox chemistry raises significant mechanistic issues as to how these amino acids are activated toward radical chemistry in a controlled manner. De novo protein design has been used to examine the structural basis for the creation and maintenance of a tryptophanyl radical in a three-helix bundle protein maquette. Here we report the detailed structural analysis of the protein by multidimensional NMR methods. An interesting feature of the structure is an apparent pi-cation interaction involving the sole tryptophan and a lysine side chain. Hybrid density functional calculations support the notion that this interaction raises the reduction potential of the W degrees /WH redox pair and helps explain the redox characteristics of the protein. This model protein system therefore provides a powerful model for exploring the structural basis for controlled radical chemistry in protein.
authors.affiliation: The Johnson Research Foundation and Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6059, USA.
authors.forename: Qing-Hong
authors.initials: QH
authors.lastname: Dai
authors.forename: Cecilia
authors.initials: C
authors.lastname: Tommos
authors.forename: Ernesto J
authors.initials: EJ
authors.lastname: Fuentes
authors.forename: Margareta R A
authors.initials: MR
authors.lastname: Blomberg
authors.forename: P Leslie
authors.initials: PL
authors.lastname: Dutton
authors.forename: A Joshua
authors.initials: AJ
authors.lastname: Wand
mesh_terms: D004798:Enzymes / Q000737:chemistry*; D004926:Escherichia coli / Q000378:metabolism; D008239:Lysine / Q000737:chemistry; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010084:Oxidation-Reduction; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*
chemical_list: D004798:Enzymes; D011506:Proteins; D008239:Lysine