Figure 3. Kappa receptor with morphine. Panel A, view from the side showing placement of ligand in the receptor. 

 Panel B, view from extracellular space showing placement of ligand in the helical bundle. Panel C, close-up of ligand 

 and residues in the receptor. Hydrogen bonds are shown as dotted lines. 



a small variation, either valine or isoleucine. 

 Again, neither residue would produce a large 

 change in size or charge. However, Trp382, in 

 mu, is either Tyr312 in kappa or LeuSOO in 

 delta. This mutation changes the size and 

 charge at this location. The kappa and mu 

 complexes both have the residue within 3 A 

 of morphine. The variance between our model 

 and the model by Strahs and Weinstein (1997) 

 might be due to the projection map of bovine 

 rhodopsin and how the helices were oriented 

 by these researchers. 



In another study, a series of chimeric recep- 

 tors was expressed and binding of morphine 

 was determined by Fukuda et al. (1995), who 

 reported that helices 5-7 were needed for mu 

 type binding. In our study, we found that mor- 

 phine binds to residues in helices 3 (Asp211), 

 6 (His361) and 7 (Ser381). The residues in 

 heUces 3 and 6 are found in all three receptor 

 complexes at the same location and therefore 

 were not indicated as selective for one recep- 

 tor. However, we found a large variation of 



aromatic interactions for the three receptors. 

 We propose that these differences do account 

 for the differences in the binding profiles in 

 the opioid receptors. The mu/morphine com- 

 plex has aromatic interactions with helices 5 

 and 7. The kappa/morphine complex has aro- 

 matic interactions with heUces 3, 5, 6, and 7. 

 Finally the delta/morphine complex only has 

 aromatic interactions with helix 3. These re- 

 sults indicate that the model agrees with the 

 mutagenesis of Fukuda et al. (1995). 



A mutagenesis study by Befort et al. (1996) 

 examined the role of aromatic transmembrane 

 residues to determine the role these residues 

 played in the binding of various ligands and 

 the delta opioid receptor. They concluded that 

 Try 129 contributed a large part of the Hgand 

 binding in the mouse delta opioid receptor. 

 They further stated that there is likely a gen- 

 eral binding domain but that each ligand will 

 bind uniquely. In our work, we found that the 

 three receptor models all had interactions with 

 morphine and aspartic acid in helix 3 and his- 



