ORGANIC-CHEMISTRY FOR STRUCTURAL BIOLOGY - PROBING THE FUNCTIONAL STRUCTURE OF PROTEINS BY PHOTOAFFINITY-LABELING

Based on the recent development of recombinant techniques, the investi gation of biofunctional machinery at their ligand accepting interfaces has become a challenging and important subject of organic chemistry i n the oncoming new century. Three major approaches currently used for structural biology have their own advantages and limitations. Spectros copic methods are useful for analyzing ligand-receptor interactions at the atomic level. These approaches, however,: usually require a signi ficant amount of stable and pure proteins. Protein engineering based o n gene technologies provides a series of mutants for the structural an alysis of functional sites. One prerequisite for the use of this metho ds is that the mutants must, to a large extent, retain the conformatio n of the native receptors. Photoaffinity labeling, one of the third in dependent approach, has become increasingly appreciated as a powerful chemical methodology for the detailed structural analysis of ligand bi nding domains. The technique of photoaffinity labeling is a reliable c hemical method which should be considered as being complementary to, r ather than in competition with, the other two approaches. This review is focusing the recent application of photoaffinity labeling for probi ng the functional structure of ion channels, receptors, and enzymes.