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

J H Viles, S U Patel, John Blayney Owen Mitchell, C M Moody, D E Justice, J Uppenbrink, P M Doyle, C J Harris, P J Sadler, J M Thornton

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

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 H-1 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' 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. (C) 1998 Academic Press Limited.

Original languageEnglish
Pages (from-to)973-986
Number of pages14
JournalJournal of Molecular Biology
Volume279
Issue number4
Publication statusPublished - 19 Jun 1998

Keywords

  • beta-turn mimetics
  • peptide design
  • zinc fingers
  • solution structure
  • H-1 NMR
  • ENHANCER BINDING-PROTEIN
  • CRYSTAL-STRUCTURE
  • DNA RECOGNITION
  • HIGH-RESOLUTION
  • SECONDARY STRUCTURE
  • NMR-SPECTROSCOPY
  • CHEMICAL-SHIFTS
  • GRAMICIDIN-S
  • AMINO-ACID
  • COMPLEX

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