ABSTRACT
Proteins: COREX/BEST................................................................ 351 15.3 Conclusions ................................................................................................. 356 Acknowledgment ................................................................................................... 357 References .............................................................................................................. 358
The ability of proteins to couple the binding of a ligand at one site of a macromolecule or macromolecular complex to the regulation of another nonoverlapping site is known as allostery. This functional property of proteins was rst observed more than 100 years ago [1], and has been studied intensively since [2-5]. Early efforts to understand allostery focused on the development of phenomenological models to explain the observed coupling between sites located in symmetrically arranged monomers of homo-oligomeric systems [6,7], in which oxygen binding in hemoglobin received the most attention [3,8-10]. Although the different models initially provided no physical insight into the origins of the allosteric coupling energies, the subsequent availability of structures for various ligated states of hemoglobin [11] led to a seemingly important connection. Namely that the physical basis of allosteric control could be reconciled in the context of the atomic-level changes in the bonds that are made or broken in conversion between the various states of the protein or the quaternary structures of the oligomer [11-13]. Indeed, numerous protein systems have been observed to behave in a manner consistent with a structural-mechanical basis of allosteric control between coupled sites [14,15], suggesting that an exclusively structural representation provides a useful framework for understanding allostery,
albeit qualitatively. What has not been established, however, is that such a framework provides a suitable set of organizing principles within which an understanding of allosteric phenomena in one system can be ascertained from data obtained in another. In short, will a structure-based description of allostery that focuses on identifying and characterizing pathways between allosteric sites provide a quantitative, predictive model?
