Protein binding site/cavity

In a first step, INH was extracted from the binding site cavity and a commercial docking program (FlexX [16]) was applied to control whether the original binding pose of the X-ray structure could be re-found. For this calculation not the complete protein but only a volume with a radius of 10 A around the binding site was considered. 

Heptahelical domains are protein modules found in all known G-protein coupled receptors, made up of seven transmembrane helices interconnected by three extra and three intracellular loops. For most G-protein coupled receptors activated by small ligands, the binding site is located in a cavity formed by transmembrane domains 3, 5, 6 and 7. 

Fig. 3. Close-up view of the L-Arg binding site and surrounding protein structure. Note the sheet structure forming the roof of the active site, which is distinct from peroxidases and P450s, where hehcal structures form the distal cavity. Note, too, the H-bonds between the Cys hgand, Trp 180, and a peptide NH group. Donation of two H-bonds to the Cys ligand is a common feature found in other iron-thiolate proteins.

Fig. 2. QSURF protein surface from FLO-QXP around ligand in the hinge region of the ATP binding site of a kinase. The scaffold makes two hydrogen bonds with the protein backbone (hinge). The micro-cavity on the right of the iigand dot circle) is created by three atoms in the vicinity, the iines of singuiarity in the moiecuiar surface resuits of the intersection between two protein atoms. The three color code of the protein surface corresponds to the hydrophobic area (yelloWi or negative and positive polar areas (Woe and red, respectively).

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