Side-chain interactions between sulfur-containing amino acids and phenyalanine in .alpha.-helixes

Abstract

The side-chain-side-chain interaction between Phe residues and sulfur-containing residues (Cis and Met) in the two possible orientations at positions i, i + 4 of alpha-helices is described. We have analyzed the contribution to helical stability of the above interactions by studying eight polyalanine-based peptides differing at the residues at positions 9 and 13. These two positions were independently mutated from Ala (AA), to Cys (AC and CA), Met (AM and MA), and Phe (AF and FA) and to the pairs Phe-Met (FM), Met-Phe (MF), Phe-Cys (FC), and Cys-Phe (CF). The intrinsic helical propensities of Cys, Met, and Phe were found to be those previously described in the algorithm AGADIR. NMR analysis of the FM, MF, FC, and CF peptides showed the formation in aqueous solution of contacts between the aromatic ring and the side chains of Cys or Met, at the two i, i + 4 orientations. CD studies demonstrated the important contribution of two of these interactions (FM and FC) to alpha-helix stability (up to 2 kcal mol-1 in the Phe-Cys pair). Statistical analysis of the protein database provides a rationale for the stereospecificity and free energies of the interactions. The very favorable interaction between an aromatic ring and a sulfur-containing amino acid explains why in the protein database around 50% of the sulfur atoms are contacting aromatic rings (Reid et al., 1985).

Addition of side chain interactions to modified Lifson‐Roig helix‐coil theory: Application to energetics of Phenylalanine‐Methionine interactions

“…The interaction energies found by AGADIR from globally fitting data on peptides are given as -0.3 kcal.mol-' for Phe-Met and -0.0 kcal.mol-' for Met-Phe in Muiioz and Serrano (1994) and -0.4 kcal.mol-l for Phe-Met and -0.2 kcal.mol-' for Met-Phe in Muiioz and Serrano (1995). Both these sets of results differ from the results found here and by Viguera and Serrano (1995 Serrano [1995]). The authors were, therefore, forced to assume that many side chain interactions have identical free energies.…”

“…In the peptides studied here, the interaction between Phe and Met is the only side chainside chain interaction present in the helix, allowing the free energy of this interaction to be accurately determined. The measured free energies (-0.75 kcal.mol" and -0.54 kcal.mol-l for the Phe-Met and Met-Phe orientations, respectively) are slightly larger than the interaction energies determined by Viguera and Serrano (1995) for similar interactions in peptides containing several different side chain-side chain interactions analyzed with AGADIR (Muiioz & Serrano, 1994). Muiioz and Serrano's results (-0.65 0.15 kcal.mol-' for Phe-Met and -0.20 -t 0.2 kcal.mol-l for Met-Phe) may differ principally as a result of using AGADIR (see discussion below).…”

“…is the grateful recipient of a BBSRC (UK) studentship. We thank Tod Klingler, Robert Baldwin, Luis Serrano, and Beatrice Huyghes-Despointes for helpful discussions and Luis Serrano for a preprint of Viguera and Serrano (1995). This work was supported by grants from the BBSRC (SC103358) and the Royal Society (574005.G501).…”

“…The behavior of such molecules indicates that helix stability is a function of the intrinsic helix-forming tendencies of constituent amino acids ; reviewed by Scholtz et al, 1991;, capping preferences at the carboxyl and amino termini (Presta & Rose, 1988;Richardson & Richardson, 1988;Serrano & Fersht, 1989;Lyu et al, 1992;Forood et al, 1993;Doig et al, 1994;Doig & Baldwin, 1995), and specific side chain-side chain interactions. These side chain interactions include salt bridges (Marqusee & Baldwin, 1987;Lyuetal., 1989;Andersonetal., 1990;Fairmanetal., 1990;Horovitz et al, 1990;Cans et al, 1991;Stellwagen et al, 1992;HuyghuesDespointes et al, 1993;Scholtz et al, 1993), hydrogen bonds Huyghues-Despointes et al, 1995), and hydrophobic interactions Armstrong et al, 1993;Padmanabhan & Baldwin, 1994a, 1994bViguera & Serrano, 1995). Charged residues may also interact with the helix-dipole (Hol et al, 1978;Armstrong et al, 1993;HuyghuesDespointes et al, 1993;Scholtz et al, 1993), but these energies are partly subsumed into capping preferences (Doig et al, 1994).…”

Caracterización de la estructura secundaria de subtipos de la histona H1 por dicroísmo circular

“…La región amida da información sobre la organización estructural de una proteína y es usada para caracterizar la estructura secundaria y sus cambios; por ejemplo, la estructura en hélice-alfa muestra un fuerte y característico espectro en la región del UV lejano. Por tanto, a partir de los espectros de DC en la región amida, se pueden utilizar varios modelos matemáticos para determinar la estructura secundaria de las proteínas (29)(30)(31)(32).…”