Integrative Structural Biology of Enzyme Active Sites

Abstract

This chapter focuses on the integrative structural biology of enzyme active sites. Structure plays a critical role in shaping our understanding of the chemistry that takes place within enzyme active sites, and integrative techniques that couple solid-state NMR with diffraction and computation have been shown to be highly effective at highlighting this chemistry by determining the structure with atomic resolution. This chapter takes as a detailed example the integrative approach of NMR crystallography applied to tryptophan synthase, along with a select group of additional examples that feature distinct approaches for combining ssNMR with other structural, biochemical, and mechanistic data. These studies share the overall goal of merging global and local restraints to provide structures with atomic resolution that shed new light on the chemistry, mechanism, and functional control of enzyme catalysis.