Scaffolds, structural homologous proteins

S. J. Benkovic, Rational design of a scyt-alone dehydratase-like enzyme using a structurally homologous protein scaffold, Proc. Natl. Acad. Sci. USA 1999, 96(7), 3568-3571. 

Homologous proteins have similar three-dimensional structures. They contain a core region, a scaffold of secondary structure elements, where the folds of the polypeptide chains are very similar. Loop regions that connect the building blocks of the scaffolds can vary considerably both in length and in structure. From a database of known immunoglobulin structures it has, nevertheless, been possible to predict successfully the conformation of hyper-variable loop regions of antibodies of known amino acid sequence. 

The above examples of peptide scaffold- or nonpeptide template-based peptidomimetic agonists or antagonists illustrate various strategies to elaborate bioactive conformation and/or pharmacophore models of peptide ligands at their receptors. In many cases, receptor subtype selectivity has also been achieved by systematic structural modifications of prototypic leads of peptidomimetics. Thus, although the 3D structures of G-protein-coupled receptors (GPCRs) remain as elusive (except for models constructed from homology-based low-... 

---