Three-dimensional profiles from residue-pair preferences: Identification of sequences with β/α-barrel fold

Abstract

The three-dimensional profile method expresses the three-dimensional structure of a protein as a table, the profile, which represents the local environment of each residue. The score of an amino acid sequence, aligned with the three-dimensional profile, reflects its compatibility with the profiled structure. In the original implementation, each local environment was characterized by its polarity, the area buried of its side chain, and its secondary structure. Here we describe a modified three-dimensional profile algorithm that characterizes the local environment in terms of the statistical preferences of the profiled residue for neighbors of specific residue types, main-chain conformations, or secondary structure. Combined profiles of the original and the three new types were tested on β/α-barrel protein structures. The method identified the following enzymes of unknown three-dimensional structure as probable β/α-barrels, all of which catalyze reactions in the biosynthesis of aromatic amino acids: anthranilate phosphoribosyltransferase (trpD), glutamine aminotransferase (trpG), and phosphoribosylformimino-5-aminoimidazole carboxamide ribotide isomerase (hisA).