Two groups and three classes of the conserved structural organization of nucleophile and non-canonical ElbowFlankOxy networks in different superfamily proteins.

Abstract

The nucleophile elbow is a well-known structural motif, which exists in proteins with catalytic triads and contains a catalytic nucleophile and the first node of an oxyanion hole. Here, we show that structural similarities of proteins with the nucleophile elbow extend beyond simple nucleophile elbow motifs. The motifs are incorporated into larger conserved structural organizations, the ElbowFlankOxy networks, incorporating motifs and flanking residues and networks of conserved interactions. A detailed structural analysis shows two major types of ElbowFlankOxy networks, depending on the formation of the oxyanion hole. Additionally, the ElbowFlankOxy networks show three classes: Class 1-2-3, 3-1-2, and 2-3-1, defined by the order in which the catalytic nucleophile and key interacting residues are located in the amino acid sequence, giving rise to six ElbowFlankOxy network variations. This makes it possible to properly position homologous non-catalytic, non-standard, and unusual catalytic triad active sites of proteins with the nucleophile elbow within the fold classification.