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Disulfide Bonds versus Trp⋅⋅⋅Trp Pairs in Irregular β‐Hairpins: NMR Structure of Vammin Loop 3‐Derived Peptides as a Case Study
Author(s) -
Mirassou Yasmina,
Santiveri Clara M.,
Pérez de Vega M. Jesús,
GonzálezMuñiz Rosario,
Jiménez M. Angeles
Publication year - 2009
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200800834
Subject(s) - chemistry , disulfide bond , loop (graph theory) , nuclear magnetic resonance spectroscopy , peptide , stereochemistry , crystallography , biochemistry , mathematics , combinatorics
Where a noncovalent interaction is better than a covalent bond : The most stabilising cross‐strand pairs were incorporated into an irregular β‐hairpin, loop 3 of vammin. 1 H and 13 C NMR conformational analyses of these designed peptides indicated that an edge‐to‐face Trp⋅⋅⋅Trp interaction leads to a β‐hairpin that is more stable than a disulfide bond.Structural studies on model peptides have led to a good understanding of the rules behind the formation and stability of regular β‐hairpins. To test their applicability to the successful design of irregular β‐hairpins with long loops and/or β‐bulges at the strands, we mimicked loop 3 of vammin, a 4:6 β‐hairpin with a non‐Gly β‐bulge. The most stabilising cross‐strand pairs, disulfide bonds or/and Trp⋅⋅⋅Trp pairs, were incorporated at non‐hydrogen‐bonded sites in peptides spanning the 69–80 region of vammin. According to NMR data, these modified peptides adopt β‐hairpin conformations as intended by design. The Trp‐containing peptides reproduce even the unusual positive ϕ angle for the Gln residue, with the indole rings in the preferred edge‐to‐face orientation. For the first time the β‐hairpin‐stabilising capacities of a disulfide bond and a Trp⋅⋅⋅Trp pair are compared in the same model system. We found that the contribution to stability of the noncovalent indole–indole interaction is larger than that of the covalent disulfide bond, and that their combination gives rise to an even more stable β‐hairpin.