title: Design, synthesis and structure of a zinc finger with an artificial beta-turn.
abstract: We have incorporated a bicyclic beta-turn mimetic (BTD; beta-turn dipeptide) into a zinc finger, creating a zinc finger with an artificial beta-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 X3-Cys-X4-Cys-X12-His-X3-His-X. The peptide was designed with BTD between the chelating cysteine residues, with BTD forming a type II' beta-turn linking the two strands of a distorted anti-parallel beta-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.
authors.affiliation: Department of Chemistry, Birkbeck College, University of London, Gordon House, London, WC1H 0PP, UK.
authors.forename: J H
authors.initials: JH
authors.lastname: Viles
authors.forename: S U
authors.initials: SU
authors.lastname: Patel
authors.forename: J B
authors.initials: JB
authors.lastname: Mitchell
authors.forename: C M
authors.initials: CM
authors.lastname: Moody
authors.forename: D E
authors.initials: DE
authors.lastname: Justice
authors.forename: J
authors.initials: J
authors.lastname: Uppenbrink
authors.forename: P M
authors.initials: PM
authors.lastname: Doyle
authors.forename: C J
authors.initials: CJ
authors.lastname: Harris
authors.forename: P J
authors.initials: PJ
authors.lastname: Sadler
authors.forename: J M
authors.initials: JM
authors.lastname: Thornton
mesh_terms: D000595:Amino Acid Sequence; D015195:Drug Design; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D011487:Protein Conformation; D016415:Sequence Alignment; D016335:Zinc Fingers