Design, synthesis and structure of a zinc finger with an artificial beta-turn.
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.
Viles
J H
JH
Department of Chemistry, Birkbeck College, University of London, Gordon House, London, WC1H 0PP, UK.
Patel
S U
SU
Mitchell
J B
JB
Moody
C M
CM
Justice
D E
DE
Uppenbrink
J
J
Doyle
P M
PM
Harris
C J
CJ
Sadler
P J
PJ
Thornton
J M
JM
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