Protein Structure and Function: Application of Bioinformatics Methods - John Rigden 2014

Structural Motifs
Discussion

The primary reason for using Structure/135.html">Structural motifs rather than comparing fold types is that the structural features directly involved in protein function serve as the most accurate and efficient indicators of that function. At the same inventive time, determining which specific residues are truly crucial for function is more challenging than utilizing the entire fold type. Although assumptions regarding importance can be made for residues in the immediate vicinity of the catalytic center or binding site, this approach is far from definitive. Nevertheless, as the volume of available structures grows, motif-identification Methods applied to diverse sets of positive Examples are becoming increasingly viable.

This approach shifts the analytical burden from the direct identification of individual residues to the Selection of appropriate sets of structures that yield insight into biological Functions.

What constitutes the most natural Protein Classification from the perspective of such "fine-structure" motifs? In Enzymes, individual residues or functional groups play distinct roles throughout the reaction process: substrate recognition, catalysis of specific reaction steps, stabilization of intermediates, or some combination thereof. As Proteins evolve to perform novel functions—to complicate matters further—they may co-opt existing local structural features responsible for partial functions common to both their ancestral and current roles (Babbitt and Gerlt 2000; Bartlett et al. 2003). This partly explains why members of homologous yet divergent enzyme groups frequently share identical configurations of a small number of Amino Acids, despite catalyzing overall disparate reactions. In the case of enzymes, one can conceptualize a hierarchy of motifs comprising patterns linked to partial functions shared across a diverse group, alongside more complex patterns corresponding to the complete reaction catalyzed by more closely related proteins. Consequently, a natural classification scheme should incorporate levels for homologous groups sharing a common partial function and the specific structural features (structural motifs) associated with it (Babbitt 2003). Presumably, functions involving small-molecule binding can be described similarly, with Ligand substructures playing a role analogous to partial functions. Moreover, ligand binding is rarely an exhaustive description of function, and additional structural elements may be coupled to conformational changes or the recognition of other molecules upon ligand binding.

The difficulty in establishing such a structure-based functional classification underscores The Need for more detailed information regarding structures and enzymatic mechanisms in order to determine which partial functions have proved more evolutionarily conserved than others.