Aromatic side-chain interactions in proteins: near- and far-sequence Tyr-X pairs

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.