Human 5-HT3A -- Trp 90

Species Original Mutated to Mutation
Human Trp 90  

 

Rat Equivalent Trp 89    
Mouse Equivalent Trp 95

Ala

Tyr

Ser

W95A

W95Y

W95S

 

mTrp95Ala

Nine residues (Thr 86, Thr 87, Tyr 88, Ile 89, Tyr 91, Arg 92, Gln 93, Tyr 94, Trp 95) were mutated individually to alanine (alanine scanning mutagenesis). The ligands [3H]granisetron, curare, and serotonin were used to examine the properites of the 5-HT3 binding site.

W90F was analyzed instead of W90A, and it proved to be the only one that significantly affected the interaction of curare with the receptor. R92A was the only substitution that altered the affinity of the agonist serotonin. W90F, R92A, and Y94A all reduced the affinity of [3H]granisetron. The periodicity of the effect suggests the involvement of a beta-strand.

 

Yan D, Schulte MK, Bloom KE, White MM (1999) Structural Features of the Ligand-binding Domain of the Serotonin 5HT3 Receptor. The Journal of Biological Chemistry 274 (9): 5537-5541

 

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mTrp95Tyr

No specific binding of either [3H]granisetron or [3H]mCPBG was observed with this mutant. When transfected into HEK293 cells, the mutant had no electrophysiological response even to high concentrations of 5-HT.

 

Spier AD, Lumis SCR (2000) The Role of Tryptophan Residues in the 5-Hydroxytryptamine3 Receptor Ligand Binding Domain. The Journal of Biological Chemistry 275(8): 5620-5625

 

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mTrp95Ser

No specific binding of either [3H]granisetron or [3H]mCPBG was observed with this mutant. When transfected into HEK293 cells, the mutant had no electrophysiological response even to high concentrations of 5-HT.

 

Spier AD, Lumis SCR (2000) The Role of Tryptophan Residues in the 5-Hydroxytryptamine3 Receptor Ligand Binding Domain. The Journal of Biological Chemistry 275(8): 5620-5625

 

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