Effects of i and i+3 residue identity on Cis-Trans isomerism of the aromatici+1-prolyli+2 amide bond: Implications for type VI β-turn formation

• Published in: Biopolymers 2006, Vol.84 (2), p.192-204
• Main Authors: Meng, Hai Yun, Thomas, Krista M., Lee, Aaron E., Zondlo, Neal J.
• Format: Article
• Language: English
• Subjects: aromatic-aromatic interaction; aromatic-prolyl interaction; cis-trans isomerization; proline; type VI β-turn
• ISSN: 0006-3525; 1097-0282
• DOI: 10.1002/bip.20382

Cis–trans isomerization of amide bonds plays critical roles in protein molecular recognition, protein folding, protein misfolding, and disease. Aromatic–proline sequences are particularly prone to exhibit cis amide bonds. The roles of residues adjacent to a tyrosine–proline residue pair on cis–trans isomerism were examined. A short series of peptides XYPZ was synthesized and cis–trans isomerism was analyzed. Based on these initial studies, a series of peptides XYPN, X = all 20 canonical amino acids, was synthesized and analyzed by NMR for i residue effects on cis–trans isomerization. The following effects were observed: (a) aromatic residues immediately preceding Tyr–Pro disfavor cis amide bonds, with Ktrans/cis= 5.7–8.0, W > Y > F; (b) proline residues preceding Tyr–Pro lead to multiple species, exhibiting cis–trans isomerization of either or both X–Pro amide bonds; and (c) other residues exhibit similar values of Ktrans/cis (= 2.9–4.2), with Thr and protonated His exhibiting the highest fraction cis. β‐Branched and short polar residues were somewhat more favorable in stabilizing the cis conformation. Phosphorylation of serine at the i position modestly increases the stability of the cis conformer. In addition, the effect of the i+3 residue was examined in a limited series of peptides TYPZ. NMR data indicated that aromatic residues, Pro, Asn, Ala, and Val at the i+3 residue all favor cis amide bonds, with aromatic residues and Asn favoring more compact ϕ at Tyrcis and Ala and Pro favoring more extended ϕ at Tyrcis. D‐Alanine at the i+3 position particularly disfavors cis amide bonds. © 2005 Wiley Periodicals, Inc. Biopolymers 84: 192–204, 2006 This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at [e-mail]