Cover Picture (Angew. Chem. Int. Ed. Engl. 9/1995)

The cover picture shows a section of a ligand–receptor complex determined by multidimensional NMR spectroscopy. This complex is formed from Arg‐Lys‐Leu‐Pro‐Pro‐Arg‐Pro‐Ser‐Lys (white; blue = N, red = O) and the Src Homology 3 (SH3) domain of phosphatidylinositol 3‐kinase (P13K; the protein backbone is shown as a red tube, selected amino acid residues are red or yellow). Combinatorial chemistry demonstrated that the first of three binding pockets of the PI3K SH3 domain binds Arg residues (not shown) and that the second pocket recognizes Leu‐Pro dipeptide elements. The third binding site is formed from conserved tyrosine residues (red) and a glutamic acid group (yellow) and selectively binds Arg‐Pro sequences with formation of a salt bridge between Arg and Glu (bottom left). J. K. Chen and S. L. Schreiber describe how they arrived at this detailed analysis of protein‐ligand interactions on pp. 953ff.