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Sculpting Metal‐binding Environments in De Novo Designed Three‐helix Bundles
Author(s) -
Plegaria Jefferson S.,
Pecoraro Vincent L.
Publication year - 2015
Publication title -
israel journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.908
H-Index - 54
eISSN - 1869-5868
pISSN - 0021-2148
DOI - 10.1002/ijch.201400146
Subject(s) - chemistry , histidine , helix bundle , carbonic anhydrase , metalloprotein , peptide , protein design , cysteine , metal , tris , active site , combinatorial chemistry , stereochemistry , biochemistry , enzyme , protein structure , organic chemistry
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 α 3 D, a de novo designed three‐helix bundle peptide with a well‐defined fold. We will then cover our recent work in functionalizing the α 3 D 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 α 3 D framework.