In Vitro Selected Macrocyclic Peptides: Tools for Regulating the Conformational Freedom of Transmembrane Proteins.

In Vitro Selected Macrocyclic Peptides: Tools for Regulating the Conformational Freedom of Transmembrane Proteins. Yakugaku Zasshi. 2016;136(2):191-6 Authors: Hipolito CJ, Nishio K, Suga H Abstract   Membrane proteins allow a cell to communicate with its environment by relaying a signal or transporting a molecule through the cell membrane. Elucidation of the three-dimensional structure of a membrane protein provides a greater understanding of its function and mechanisms. Ultimately, this knowledge will enlighten researchers on how these proteins can be regulated to elicit a desired cellular response, which could lead to novel therapeutic medicine. Unfortunately, the determination of the high-resolution crystal structures of transmembrane proteins remains a challenge due to their poor solubility and high conformational flexibility. Additives and cocrystallization ligands are being used to address these problems. In vitro selected macrocyclic peptides have recently been successfully employed as cocrystallization ligands. Although originally intended as inhibitors and drug lead molecules, in vitro selected macrocyclic peptides are now showing that their pharmacodynamic properties also allow them to serve as excellent cocrystallization ligands. Structures for macrocyclic peptide-bound transporters, the multidrug and toxic compound extrusion family transporter from Pyrococcus furiosus (PfMATE) and the ABC transporter subfamily B member ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - Category: Drugs & Pharmacology Authors: Tags: Yakugaku Zasshi Source Type: research