Opioid Receptor Models — Baiitista, Ashen and Carjjenter 



115 



X^His361 



Ser381 



Figure 4. Delta 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. 



Table 5. Analysis of data presented by Strahs and Wein- 

 stein 1997. Residues listed are in the human mu opioid 

 receptor. Residues that the mu model indicates are inward 



facing are 



in bold. 





Helix 



Residues 



Orientation 



1 



Metl36 



Towards other helices 





Csyl43 



Towards other helices 



2 



AlalSl 



Inward facing 





Leu 185 



Towards other helices 





Asnl91 



Outward facing 



3 



Ile208 



Outward facing 



4 



Leu264 



Outward facing 



5 



Ile302 



Towards other helices 



6 



Val364 



Inward facing 





Lys367 



Extracellular surface 



7 



Gln378 



Extracellular surface 





Thr379 



Extracellular surface 





Trp382 



Inward facing 





His383 



Towards other helices 



tidine in helix 6. We also noted that Tryl29 in 

 the delta receptor was within 3 A of moiphine. 



In a second study, the same group investi- 

 gated the importance of residues Asp 128, 

 Tyrl29, and Tyr308 in the mouse delta opioid 

 receptor (Befort et al. 1999). They found that 

 mutation of any of these three residues caused 

 an agonist independent activation of the re- 

 ceptor. In our study, Asp 128 is involved in hy- 

 drogen bonding with moi'phine. We also found 

 that Tyrl29 was within 3 A of moq^hine. 

 Tyr308 (also 308 in human delta receptor) ap- 

 pears to be involved in helical packing and in- 

 teracts in helix 1 with Tyr56, Val59, and Gly63, 

 and in helix 2 with Asp94, Ala98, and Thr99. 

 The mutation of this residue would affect the 

 packing of the heUcal bundle and could result 

 in constitutively active receptor. 



A site-directed mutagenesis study (Mansour 

 et al. 1997) attempted to determine the resi- 

 dues lining the binding site of the mu opioid 

 receptor. Two key residues were indicated to 



