This protein is a 99 amino acids homodimeric aspartic protease and its substrate-binding pocket includes the D25-T26-G27 candlytic triad and flap regions, which presumably open and close to allow entry and binding of substrates or inhibitors [ 22, 23].
Approaches to identify binding pockets include geometric analyses of protein surfaces, comparisons of protein structures, similarity searches in databases of protein cavities, and docking scans to reveal areas of high ligand complementarity.
In contrast to the TTR∶11 structure, all protomer residues of the binding pocket, including Lys15, were well ordered in the electron density map.
Residues that experienced the largest changes in relaxation behavior surround the phosphopantetheine attachment site and form the entrance to the fatty acid binding pocket, including S32, G35, S38, L39, and T41.
Our studies focused on three amino acids in the substrate binding pocket including W102β, Y154β, and Y205β.
Other hydrophobic residues in the retinal binding pocket, including Phe 120 and Phe 188 are specific to cephalopod rhodopsin and are not conserved in vertebrate rhodopsin.
The mutations resided throughout the cap-binding pocket, including residues on the β1 β2 loop, and on and between the β1, β3, β5 and β6 strands with side-chains shown in the crystal structure to extend into the cap-binding pocket (Figure 1 A and B; 5 A D).
The 3-dimensional structure of Dfr (PDB ID: 2W3V) depicting the active site pocket including the two important residues (positions 28 and 94) for TMP binding was analysed.
The structures of IPK in complex with IP and IPP define the secondary structural elements comprising the IP-binding pocket and include the β2−αB glycine-rich loop, the αB helix, the β3−β4 hairpin, the β4−αC loop, the N-terminal section of the αC helix, and the β9−β10 hairpin (4, panel a).
The resulting model generated by this analysis (fig. 5) reveals a ligand-binding pocket that includes the 4th and 5th TM regions and second extracellular loop, compatible with the regions of amino acid differentiation described earlier for the α and β lineages.
