Sandbox Reserved 1095: Difference between revisions
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=== Recent studies === | === Recent studies === | ||
Finally, around 2015, researchers have found the crystal structure of the receptor in complex with its antagonist [https://pubchem.ncbi.nlm.nih.gov/compound/ZD-7155-hydrochloride ZD7155] and with an inverse agonist [https://en.wikipedia.org/wiki/Olmesartan olmesartan]<ref> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4705918/ </ref>. [https://en.wikipedia.org/wiki/X-ray_crystallography X-ray cryogenic-crystallography] has been used. They have found similar conformation of the receptor when it is linked to the antagonist or to the inverse agonist. They have also found conserved molecular recognition modes. To complete this discovery, they have realized some experiments with mutants to identify the different residues which interact with the ligand. | Finally, around 2015, researchers have found the crystal structure of the receptor in complex with its antagonist [https://pubchem.ncbi.nlm.nih.gov/compound/ZD-7155-hydrochloride ZD7155] and with an inverse agonist [https://en.wikipedia.org/wiki/Olmesartan olmesartan]<ref name="Zhang2015"> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4705918/ Zhang H, Unal H, Desnoyer R, et al. Structural Basis for Ligand Recognition and Functional Selectivity at Angiotensin Receptor. J Biol Chem. 2015;290(49):29127–29139. doi:10.1074/jbc.M115.689000] </ref>. [https://en.wikipedia.org/wiki/X-ray_crystallography X-ray cryogenic-crystallography] has been used. They have found similar conformation of the receptor when it is linked to the antagonist or to the inverse agonist. They have also found conserved molecular recognition modes. To complete this discovery, they have realized some experiments with mutants to identify the different residues which interact with the ligand. | ||
The structure of this protein have also been solved using an other method called serial femtosecond crystallography, corresponding to the structure [http://proteopedia.org/wiki/index.php/4yay 4YAY]. | The structure of this protein have also been solved using an other method called serial femtosecond crystallography, corresponding to the structure [http://proteopedia.org/wiki/index.php/4yay 4YAY]. | ||
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[https://en.wikipedia.org/wiki/Olmesartan Olmesartan] anchored to ATR1 by the residues <scene name='82/829348/Tyr35/6'>Tyr 35</scene>, <scene name='82/829348/Trp84/4'>Trp84</scene> and <scene name='82/829348/Arg167/3'>Arg167</scene>. | [https://en.wikipedia.org/wiki/Olmesartan Olmesartan] anchored to ATR1 by the residues <scene name='82/829348/Tyr35/6'>Tyr 35</scene>, <scene name='82/829348/Trp84/4'>Trp84</scene> and <scene name='82/829348/Arg167/3'>Arg167</scene>. | ||
Those three amino acids seem to play an important role in the binding of the drug to AT1R, thanks to the formation of extensive networks of hydrogen bonds and salt bridges with the ligand <ref name="Zhang2015" | Those three amino acids seem to play an important role in the binding of the drug to AT1R, thanks to the formation of extensive networks of hydrogen bonds and salt bridges with the ligand <ref name="Zhang2015"/>. | ||
Many drugs used to cure diseases linked with the angiotensin receptor contain a [https://en.wikipedia.org/wiki/Tetrazole tetrazole] group. Studies showed that tetrazole plays an important role in the binding with AT1R. | Many drugs used to cure diseases linked with the angiotensin receptor contain a [https://en.wikipedia.org/wiki/Tetrazole tetrazole] group. Studies showed that tetrazole plays an important role in the binding with AT1R. | ||
