title: Structure and dynamics of a primordial catalytic fold generated by in vitro evolution.
abstract: Engineering functional protein scaffolds capable of carrying out chemical catalysis is a major challenge in enzyme design. Starting from a noncatalytic protein scaffold, we recently generated a new RNA ligase by in vitro directed evolution. This artificial enzyme lost its original fold and adopted an entirely new structure with substantially enhanced conformational dynamics, demonstrating that a primordial fold with suitable flexibility is sufficient to carry out enzymatic function.
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Fa-An
authors.initials: FA
authors.lastname: Chao
authors.forename: Aleardo
authors.initials: A
authors.lastname: Morelli
authors.forename: John C
authors.initials: JC
authors.lastname: Haugner
authors.forename: Lewis
authors.initials: L
authors.lastname: Churchfield
authors.forename: Leonardo N
authors.initials: LN
authors.lastname: Hagmann
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Larry R
authors.initials: LR
authors.lastname: Masterson
authors.forename: Ritimukta
authors.initials: R
authors.lastname: Sarangi
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Veglia
authors.forename: Burckhard
authors.initials: B
authors.lastname: Seelig
mesh_terms: D000409:Alanine / Q000737:chemistry; D000595:Amino Acid Sequence; D002384:Catalysis; D020134:Catalytic Domain; D019020:Directed Molecular Evolution / Q000379:methods; D004798:Enzymes / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008670:Metals / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D015202:Protein Engineering / Q000379:methods*; D017510:Protein Folding; D011130:RNA Ligase (ATP) / Q000737:chemistry*
chemical_list: D004798:Enzymes; D008670:Metals; D011130:RNA Ligase (ATP); D000409:Alanine