P12
Structural studies of histamine receptor H1
Tian Geng, Alex Cameron, John Barker, So Iwata, and Isabel Moraes
H1 is responsible for severe allergic reactions, such as hay fever.
first‐generation: low selectivity Doxepin Pyrilamine
second‐generation: with unique carboxyl group
Crystal structure of H1 complex with doxepin revealed the doxepin binding pocket. Docking of second‐generation antagonists present interactions with the anion binding site.
(Shimamura et al. 2011)
fexofenadine Olopatadine
More need to know ?
More unique features of H1 binding pocket
Solid proof of second‐generation antagonists interact with anion binding pocket
X‐Ray crystal structure determination of H1 with a range of antagonists.
CPM 230612
1.1
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
-0.1
no ligand
Doxepin
EV5S
0
25
50
75
100
Time (min)
125
150
Crystal of H1/EV5S complex, Tested at Diamond Light Source I24
Best resolution around 4Å