Streptavidin-binding and -dimerizing ligands discovered by phage display, topochemistry, and structure-based design.
Structural and mechanistic determinants of affinity of streptavidin-binding peptide ligands discovered by phage display are reviewed along with the use of streptavidin as a paradigm for structure-based design. A novel way of producing protein-dimerizing ligands in the streptavidin model system is discussed, in which crystal packing topochemically mediates or even catalyzes dimerization of adjacent bound ligands whose reactive ligating groups are presented toward one another in productive orientations in the crystal lattice. Finally, through crystallography on a set of streptavidin complexes with small molecule and peptide ligands at multiple pHs in two space groups, the mechanism by which ligands enhance intersubunit stabilization of the streptavidin tetramer is probed.
Katz
B A
BA
Axys Pharmaceutical Corporation, South San Francisco, CA 94080, USA. brad-katz@axyspharm.com
D000595:Amino Acid Sequence; D003461:Crystallography; D019281:Dimerization; D015195:Drug Design; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D019151:Peptide Library; D011485:Protein Binding; D015202:Protein Engineering; D017434:Protein Structure, Tertiary; D019809:Streptavidin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D008024:Ligands; D009842:Oligopeptides; D019151:Peptide Library; D019809:Streptavidin