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Publication Abstract from PubMed

BACKGROUND: Small folded polypeptide motifs represented highly simplified systems for theoretical and experimental studies on protein structure and folding. We have recently reported the design and characterization of a metal-ion-independent 23-residue peptide with a beta beta alpha structure (BBA1), based on the zinc finger domains. To understand better the determinants of structure for this small peptide, we investigated the conformational role of the synthetic residue 3-(1, 10-phenanthrol-2-yl)-L-alanine (Fen) in BBA1. RESULTS: NMR analysis revealed that replacing the Fen residue of peptide BBA1 by either of the natural amino acids tyrosine (BBA2) or tryptophan (BBA3) resulted in conformational flexibility in the sheet and loop regions of the structure. This conformational ambiguity was eliminated in peptides BBA4 and BBA5 by including charged residues on the exterior of the beta hairpin designed to both select against the undesired fold and stabilize the desired structure. The evaluation of two additional peptides (BBA6 and BBA7) provided further insight into the specific involvement of the surface polar residues in the creation of well-defined structure in BBA4 and BBA5. The sequences of BBA5, BBA6 and BBA7 include only one non-standard amino acid (D-proline), which constrains a critical engineered type II' turn. CONCLUSIONS: Manipulation of residues on the exterior of small beta beta alpha motifs has led to the design of 23-residue polypeptides that adopt a defined tertiary structure in the absence of synthetic amino acids, increasing the availability and expanding the potential uses of the BBA motif. The importance of negative design concepts to the creation of structured polypeptides is also highlighted.

Design and NMR analyses of compact, independently folded BBA motifs.,Struthers M, Ottesen JJ, Imperiali B Fold Des. 1998;3(2):95-103. PMID:9565754^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.