Design, synthesis and structure of a zinc finger with an artificial β-turn

• Published in: Journal of molecular biology Vol. 279; no. 4; pp. 973 - 986
• Main Authors: Viles, John H., Patel, Sunil U., Mitchell, John B.O., Moody, Claire M., Justice, David E., Uppenbrink, Julia, Doyle, Paul M., Harris, C.John, Sadler, Peter J., Thornton, Janet M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 19-06-1998
• Subjects: 1H NMR; Amino Acid Sequence; Drug Design; Humans; Magnetic Resonance Spectroscopy; Molecular Sequence Data; peptide design; Protein Conformation; Sequence Alignment; solution structure; Zinc Fingers; β-turn mimetics; β-turn mimetics; BTD 7,8-3YY; NOE; zinc fingers; 3YY1; ROESY; 1H NMR; RMSD; TOCSY; ppm; PDB; Zn-3YY1; BTD; DQF-COSY; peptide design; solution structure; NOESY; Zn-BTD 7,8-3YY1
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1006/jmbi.1998.1764

We have incorporated a bicyclic β-turn mimetic (BTD; β-turn dipeptide) into a zinc finger, creating a zinc finger with an artificial β-turn. The designed peptide chelates zinc and has the same fold as the unmodified native zinc finger (finger 3 of the human YY1 protein). A combination of
1H NMR and structure calculations reveals that, in solution, this zinc finger has a fold similar to the known wild-type crystal structure and to other zinc fingers containing the consensus sequence X
3-Cys-X
4-Cys-X
12-His-X
3-His-X. The peptide was designed with BTD between the chelating cysteine residues, with BTD forming a type II′ β-turn linking the two strands of a distorted anti-parallel β-sheet. The C-terminal portion of the peptide forms a helix with zinc co-ordinating histidine residues on successive turns of the helix. This work represents a step towards developing methods by which parts of a target protein may be replaced by peptide mimetics.