Exploring Protein-Ligand and Protein-Protein Interactions
In this chapter, we will explore how two intracellular proteins bind their respective ligands and observe the ensuing conformational changes. The first protein is p21ras, a molecule that binds guanosine diphosphate (GDP) in the ground state and guanosine triphosphate (GTP) in the activated state. It is of therapeutic interest because activation can be brought about by the hormone insulin; in addition, p21ras is often mutated in human cancers. The second protein is eukaryotic initiation factor (eIF) 4E, a protein that recognizes the 7-methyl-G(5′)ppp(5′) cap structure on the 5′ end of eukaryotic mRNA molecules. It also responds to insulin stimulation, and there is evidence that it is a proto-oncogene. The ligands they bind are both guanosine nucleotides; however, we will see that the folds of the proteins and their interactions with the ligands differ. We will also observe the consequences of binding or exchanging ligands and visualize how the proteins form complexes with their specific macromolecular interaction partners. These investigations will illustrate basic principles from the previous four chapters and will provide you with the skills and tools required to compare structures by superposition.
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