Distribution of solvent and ligand molecules around aromatic side chains in proteins and its implication on carbonic...

Interactions between aromatic phenylalanine, tyrosine and tryptophan residues and water as well as ligand molecules were analyzed by a computer search of a large number of high resolution structures in the protein data bank. Water molecules and oxygen ligands have a preference for the edges of the aromatic residues, but the distribution of carbon ligands around the aromatic rings is different. The more hydrophilic tyrosine, followed by tryptophan, has the highest frequency of water contacts. However the situation is reversed for ligand interactions where phenylalanine is the most active of the three aromatic residues. The results indicate that hydrogen bonding by water molecules to aromatic pi-electron does not occur in protein structures. The role of the conserved Trp 209 in the catalytic mechanism of carbonic anhydrase is discussed in consideration of the results from the data base search. Normally not considered as a catalytic residue, this tryptophan is proposed to participate in the physiologically important enzymatic interconversion of carbon dioxide and bicarbonate by stabilizing substrate coordination through van der Waals' interactions.