Structural features of proteins responsible for resistance of tryptophan residues to nitrosylation.

Abstract

It is known that potentially reactive groups of the protein molecule may be most efficiently nitros(yl)ated only when located within hydrophobic globules or built into the membrane. N1-nitrosotryptophan (NOW) is a stable product of nitrosation in vitro. However, the NOW fraction in proteins is small in ordinary proteins. It suggests the existence of unknown mechanisms preventing the accumulation of NOW. Here we show that these mechanisms are underlain by the protein structure. Analysis of protein structure databases to explore the atomic surroundings of tryptophan residues revealed preferential selection of certain surroundings. N(E) atoms of tryptophan residues, which are the targets for nitrosation, have usually polar and nucleophilic groups in their environment. Residues of Asp, Glu, Cys, His, and Met act as catalysts of denitrosation (internal denitrosilase). We found that short peptides with the same residues possessed denitrosilase activity even in solution. This selection might explain both the resistance of tryptophan residues in proteins to nitrosation and the mechanisms of chemical communication by means of reversible nitrosation of proteins.