Environment of tryptophan side chains in proteins

Abstract

Although relatively rare, the tryptophan residue (Trp), with its large hydrophobic surface, has a unique role in the folded structure and the binding site of many proteins, and its fluorescence properties make it very useful in studying the structures and dynamics of protein molecules in solution. An analysis has been made of its environment and the geometry of its interaction with neighbors using 719 Trp residues in 180 different protein structures. The distribution of the number of partners interacting with the Trp aromatic ring shows a peak at 6 (considering protein residues only) and 8 (including water and substrate molecules also). The means of the solvent-accessible surface areas of the ring show an exponential decrease with the increase in the number of partners; this relationship can be used to assess the efficiency of packing of residues around Trp. Various residues exhibit different propensities of binding the Trp side chain. The aromatic residues, Met and Pro have high values, whereas the smaller and polar-chain residues have weaker propensities. Most of the interactions are with residues far away in sequence, indicating the importance of Trp in stabilizing the tertiary structure. Of all the ring atoms NE1 shows the highest number of interactions, both along the edge (hydrogen bonding) as well as along the face. Various weak but specific interactions, engendering stability to the protein structure, have been identified. Proteins 2000;38:288–300. © 2000 Wiley-Liss, Inc.