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Sculpting Metal-binding Environments in De Novo Designed Three-helix Bundles.

ABSTRACT: De novo protein design is a biologically relevant approach used to study the active centers of native metalloproteins. In this review, we will first discuss the design process in achieving ?3D, a de novo designed three-helix bundle peptide with a well-defined fold. We will then cover our recent work in functionalizing the ?3D framework by incorporating a tris(cysteine) and tris(histidine) motif. Our first design contains the thiol-rich sites found in metalloregulatory proteins that control the levels of toxic metal ions (Hg, Cd, and Pb). The latter design recapitulates the catalytic site and activity of a natural metalloenzyme carbonic anhydrase. The review will conclude with future design goals aimed at introducing an asymmetric metal-binding site in the ?3D framework.

SUBMITTER: Plegaria JS

PROVIDER: S-EPMC5771423 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Sculpting Metal-binding Environments in De Novo Designed Three-helix Bundles.

Plegaria Jefferson S JS Pecoraro Vincent L VL

Israel journal of chemistry 20150115 1

De novo protein design is a biologically relevant approach used to study the active centers of native metalloproteins. In this review, we will first discuss the design process in achieving α3D, a de novo designed three-helix bundle peptide with a well-defined fold. We will then cover our recent work in functionalizing the α3D framework by incorporating a tris(cysteine) and tris(histidine) motif. Our first design contains the thiol-rich sites found in metallore ...[more]

PMID: 29353917

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