Figure 7

3D modeling of selected NRPS AMP binding domains. A. Ribbon representation of the structure of the activated domain of Gramicidin synthetase (PDB code: 1AMU) bound to its Phe substrate (shown as a CPK model; red) and adenosine monophosphate (AMP; shown as "ball & stick" representation of the heavy atoms; light-blue). The large domain (gray ribbon), contains the substrate and AMP binding pockets. A second smaller domain (orange), involving residues D430 to F530, sits at the entrance of these pockets. "Ball & stick" representations of residues D235 and K517 are shown in green and blue, respectively. B. View of the GrsA binding pockets for Phe and AMP showing the positions of the conserved residues F234 (yellow), D235 (green), and K517 (blue). D235 and K517 are in contact with the amino and carboxyl end groups, respectively, of the Phe substrate. C. Alternative view of GrsA highlighting all the fragments of the sequence that determine the binding pockets for Phe and AMP. The amino acid composition of those fragments is listed to the right. The color convention for the residues is as follows: red and orange indicate those residues lining the substrate cavity, with residues in red making contact with the substrate Phe in the experimental structure; blue and light blue indicate residues lining the AMP binding site, with residues in blue making contact with AMP in the experimental structure. D. Slice through the substrate binding site of a 3D model of ChNPS2 module 3. The central cavity is packed with large residues that produce a shallow pocket. A ball & stick representation of a bound GLY residue is also shown to help assess the size of the cavity (compare to Fig. 7E). E. Slice through the substrate binding site of a 3D model of ChNPS2 module 4. The central cavity is lined with small residues that leading to a deep pocket. A ball & stick representation of a bound AHO is also shown to help assess the size of the cavity (compare to Fig. 7D).