Aromatic side‐chain interactions in proteins: Near‐ and far‐sequence Tyr‐X pairs

Abstract

In the present study, an extensive analysis of the aromatic Tyr-X interactions is performed on a data set of 593 PDB structures, X being Phe, His, Tyr, and Trp. The nonredundant Tyr-X pairs (2645) were retained and separated by both the residue distance in the sequence and the secondary structures they bridge. Similar to the Phe-X and His-X pairs, the far-sequence Tyr-X pairs (X partner > five apart in the sequence: 74%) show comparable secondary structures and conformers for either type of X partner, in contrast with the near-sequence Tyr-X pairs (26%). As the Phe-X pairs, the near-sequence Tyr-X pairs stabilize secondary structures, mainly the alpha- helices (positions 1, 3, and 4) and the beta-strands (position 2). Like the Phe-X and His-X pairs, most far-sequence Tyr-X pairs (34%) bridge beta-strands and only 11% bridge helices. As for the Phe-X and the His-X pairs, the X partners of the far-sequence Tyr-X pairs are frequently "above" the tyrosine ring with tilted and normal rings, whereas the X partner of the near-sequence Tyr-X pairs gradually moves from the "aside" to the "above" location, together with a progressive decrease of normal and increase of parallel rings, respectively. Unlike the His-X pairs, the interactions of the hetroatom in Tyr-X pairs are only favored with a sequence position +4 and over, owing to the spatial accessibility of the heteroatom.

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

“…The trans conformation was stabilized in peptides with X = aromatic by 0.40–0.60 kcal mol –1 relative to X = protonated His, with the largest trans stabilization induced by the most electron‐rich aromatic residue, Trp. The effect of aromatic residues on increasing K trans / cis is presumably due to the competitive interaction of the i residue aromatic ring with the aromatic ring of Tyr i +1 , which otherwise interacts with the proline ring to stabilize the cis conformation 120–123. By reducing the relative stability of the aromatic–prolyl interaction via the competitive trans ‐promoting aromatic–aromatic interaction, K trans / cis is increased.…”

Protein contacts, inter-residue interactions and side-chain modelling

“…As we showed with reduced amino acid alphabets, the use of different definitions could lead to diverging results [123]. Distribution of the privileged interactions shows expected results, like the importance of Cysteine and of aromatic residues [105,106,[124][125][126][127][128][129][130]. Specificities are found according to the distance in the sequence between residues in contact.…”

Amino acid pair- and triplet-wise groupings in the interior of α-helical segments in proteins

“…However, modest values of ΔG can make large contributions to the observed helicity of model peptides, (Smith and Scholtz, 1998) (Creamer and Rose, 1995) show relatively neutral propensities (P = 0.8 -1.3) while I-F has a positive propensity (P I-F = 1.5). On the other hand, potentially stabilizing pairs Y-W, W-W, H-F, K-F (ΔG < 0) (Andrew et al, 2002;Creamer and Rose, 1995;Fernandez-Recio et al, 1999;Meurisse et al, 2003;Meurisse et al, 2004;Thomas et al, 2002a;Thomas et al, 2002b) also show neutral propensities (P = 0.8 -1.1).…”

“…In particular for α-helices, these effects are consequence of several types of interactions between amino acid side chains -including aromatic interactions, (Butterfield et al, 2002;Meurisse et al, 2004;Thomas et al, 2002a;Thomas et al, 2002b) nonpolar/polar interactions, (Andrew et al, 2001) surface salt bridges (Iqbalsyah and Doig, 2005a;Olson et al, 2001) -and may be dependent on the relative positioning of the intervening side-chains. There is also the possibility of interactions between amino acid residue side chains and the α-helix backbone.…”