title: Rational design of nascent metalloenzymes.
abstract: Understanding the early genesis of new enzymatic functions is one of the challenges in protein design, mechanistic enzymology, and molecular evolution. We have experimentally mimicked starting points in this process by introducing primitive iron and oxygen binding sites at various locations in thioredoxin, a small protein lacking metal centers, by using computational design. These rudimentary active sites show emerging enzymatic activities that select to varying degrees between different oxygen chemistries. Even within these nascent enzymes, mechanisms by which different reactions are controlled can be discerned. These involve both stabilizing and destabilizing interactions imposed on the metal center by the surrounding protein matrix.
authors.affiliation: Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Benson
authors.forename: M S
authors.initials: MS
authors.lastname: Wisz
authors.forename: H W
authors.initials: HW
authors.lastname: Hellinga
mesh_terms: D002384:Catalysis; D004798:Enzymes / Q000737:chemistry*; D008667:Metalloproteins / Q000737:chemistry*; D008670:Metals / Q000378:metabolism; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000737:chemistry / Q000378:metabolism
chemical_list: D004798:Enzymes; D008667:Metalloproteins; D008670:Metals; D013482:Superoxide Dismutase