Effect of the N2 residue on the stability of the alpha-helix for all 20 amino acids

Citation
Dae. Cochran et Aj. Doig, Effect of the N2 residue on the stability of the alpha-helix for all 20 amino acids, PROTEIN SCI, 10(7), 2001, pp. 1305-1311
Citations number
22
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
PROTEIN SCIENCE
ISSN journal
0961-8368 → ACNP
Volume
10
Issue
7
Year of publication
2001
Pages
1305 - 1311
Database
ISI
SICI code
0961-8368(200107)10:7<1305:EOTNRO>2.0.ZU;2-S
Abstract
N2 is the second position in the cr-helix. All 20 amino acids were placed i n the N2 position of a synthetic helical peptide (CH3CO-[AXAAAAKAAAAKAAGY]- NH2) and the helix content was measured by circular dichroism spectroscopy at 273K. The dependence of peptide helicity on N2 residue identity has been used to determine a free-energy scale by analysis with a modified Lifson-R oig helix-coil theory that includes a parameter for the N2 energy (n2). The rank order of Delta DeltaG((relative to Ala)) is Glu(-), Asp(-) > Ala > Gl u(0), Leu, Val, Gin, Thr, lie, Ser, Met, Asp(0), His(0), Arg, Cys, Lys, Phe > Asn, > Gly, His(+), Pro, Tyr. The results correlate very well with N2 pr opensities in proteins, moderately well with N1 and helix interior preferen ces, and not at all with N-cap preferences. The strongest energetic effects result from interactions with the helix dipole, which favors negative char ges at the helix N terminus. Hydrogen bonds to side chains at N2, such as G in, Ser, and Thr, are weak, despite occurring frequently in protein crystal structures, in contrast to the N-cap position. This is because N-cap hydro gen bonds are close to linear, whereas N2 hydrogen bonds have poor geometry . These results can be used to modify protein stability rationally, help de sign helices, and improve prediction of helix location and stability.