Paradigms for Protein―Ligand Interactions

摘要

Protein-ligand recognition is the basis of biological and biochemical specificity and activity. Here we highlight key features of molecular recognition emerging from our structural and functional studies of several proteins with diverse specificity and activity. These proteins include calmodulin, a signal transducer for a variety of biological activities; the enzymes adenosine deaminase and aldose reductase; VP39, a vaccinia virus protein which act on both ends of mRNA; several initial high affinity receptors for bacterial ABC-type transport systems. Calmodulin's extraordinary versatility is reflected by its ability to activate numerous enzymes and structural proteins. Among the inhibitors that bind to adenosine deaminase are ground-state, reaction-coordinate and transition-state analogs. Because aldose reductase is a target for design of therapeutics to combat diabetic complications, about a thousand drugs have been synthesized which exhibit noncompetitive inhibition. To perform its function, VP39 must recognize the N7-methylguanosine cap of an mRNA transcript while also binding the transcript in a sequence-nonspecific manner. Because the transport receptors bind a variety of ligands (carbohydrates, peptides, tetrahedral oxyanions, etc.), they are a gold mine for the study of ligand recognition.