Environment of tryptophan side chains in proteins

Although relatively rare, the tryptophan residue (Trp), with its large hydr ophobic 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. A n analysis has been made of its environment and the geometry of its interac tion with neighbors using 719 Trp residues in 180 different protein structu res. The distribution of the number of partners interacting with the Trp ar omatic ring shows a peak at 6 (considering protein residues only) and 8 (in cluding water and substrate molecules also). The means of the solvent-acces sible surface areas of the ring show an exponential decrease with the incre ase in the number of partners; this relationship can be used to assess the efficiency of packing of residues around Trp, Various residues exhibit diff erent propensities of binding the Trp side chain. The aromatic residues, Me t and Pro have high values, whereas the smaller and polar-chain residues ha ve 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 interactio ns, both along the edge (hydrogen bonding) as well as along the face. Vario us weak but specific interactions, engendering stability to the protein str ucture, have been identified. (C) 2000 Wiley-Liss, Inc.