Sandbox Reserved 1095: Difference between revisions

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=== Primary and secondary structure ===

The human AT1 receptor consists of a 376 amino acid string <ref> [http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?pdbcode=4zud&template=main.html Protein Database (PDBsum): 4zud. European Bioinformatics (EBI); 2013.]</ref>. The protein is composed of

The human AT1 receptor consists of a 376 amino acid string <ref> [http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?pdbcode=4zud&template=main.html Protein Database (PDBsum): 4zud. European Bioinformatics (EBI); 2013.]</ref>. The protein is composed of <scene name='82/829348/Helix_a/1'>18 α helixes</scene> and a <scene name='82/829348/B_sheet/1'>single β sheet</scene> composed of 3 β strands. Moreover, 7 α helixes are made of a majority of hydrophobic amino acids. These helixes are long enough to cross the membrane and create a <scene name='82/829348/Transmambrane_protein/1'>hydrophobic domain</scene> which is situated into the membrane. The human angiotensin receptor is therefore an α helical trans-membrane protein.

<scene name='82/829348/Helix_a/1'>18 α ~~helix~~</scene>

and <scene name='82/829348/B_sheet/1'>3 β ~~sheets~~</scene>. Moreover, 7 α helixes are made of a majority of hydrophobic amino acids. These helixes are long enough to cross the membrane and create a <scene name='82/829348/Transmambrane_protein/1'>hydrophobic domain</scene> which is situated into the membrane. The human angiotensin receptor is therefore an α helical trans-membrane protein.

Since the angiotensin receptor belongs to the GPCRs family, those 7 α helixes contain 3 extracellular and 3 intracellular loops. The N terminus corresponds to the extracellular domain. The C terminal domain is located intracellularly.

=== Ligand binding pocket ===

In the extracellular environment, there is a β-hairpin in conjugation with <scene name='82/829348/Disulfuric_bridge/2'>two extracellular disulfure bridges</scene>. This structure is responsible for the opening and the locking of the ligand binding pocket <ref> PMID: 23386604 </ref>. The ligand goes into a <scene name='82/829348/Ligand_blinding_pocket/1'>hydrophilic pocket</scene> created into the membrane thanks to the 7 α ~~helix~~ which creates a gate between the membrane and the extracellular environment.

In the extracellular environment, there is a β-hairpin in conjugation with <scene name='82/829348/Disulfuric_bridge/4'>two extracellular disulfure bridges</scene>. This structure is responsible for the opening and the locking of the ligand binding pocket <ref> PMID: 23386604 </ref>. The ligand goes into a <scene name='82/829348/Ligand_blinding_pocket/1'>hydrophilic pocket</scene> created into the membrane thanks to the 7 α helixes which creates a gate between the membrane and the extracellular environment.

=== G protein-binding site ===

When the angiotensin II binds to the angiotensin receptor in the ligand binding pocket, the conformation of the trans-membrane domain changes to create a cytosolic cleft for the binding and activation of G proteins. In this cleft, several conserved residues can be found, which form functional motifs present in all [[GPCRs]] <ref> PMID:30608150 </ref>.

When the angiotensin II binds to the angiotensin receptor in the ligand binding pocket, the conformation of the trans-membrane domain changes to create a cytosolic cleft for the binding and activation of G proteins. In this cleft, several conserved residues can be found, which form functional motifs present in all [[GPCRs]] <ref name='Singh2019'> PMID:30608150 </ref>.

AngII mediates AT1 receptor activation via stacking interactions between Phe8(AngII)/<scene name='82/829348/His_256/2'>His256</scene>(AT1 receptor) and Tyr4(AngII)/<scene name='82/829348/Asn_111/1'>Asn111</scene>(AT1 receptor). This phenomenon results in a conformational change in transmembrane (TM)3-TM6 helixes and in interaction between TM2 and TM7.

AngII mediates AT1 receptor activation via stacking interactions between Phe8(AngII)/<scene name='82/829348/His_256/2'>His256</scene>(AT1 receptor) and Tyr4(AngII)/<scene name='82/829348/Asn_111/1'>Asn111</scene>(AT1 receptor). This phenomenon results in a conformational change in transmembrane (TM)3-TM6 helixes and in interaction between TM2 and TM7 <ref name='Singh2019'/>.

=== Interaction with drugs ===

Angiotensin Receptor Blockers (ARBs) are used to cure diseases linked to AT1R.

The ARB [https://en.wikipedia.org/wiki/Olmesartan olmesartan] is anchored to ATR1 by the residues <scene name='82/829348/Tyr35/6'>Tyr35</scene>, <scene name='82/829348/Trp84/4'>Trp84</scene> and <scene name='82/829348/Arg167/3'>Arg167</scene>.

The ARB [https://en.wikipedia.org/wiki/Olmesartan olmesartan] is anchored to ATR1 by the residues <scene name='82/829348/Tyr35/6'>Tyr35</scene>, <scene name='82/829348/Trp84/5'>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"/>.

<scene name='82/829348/3_residues_bound_to_ligand/2'>Those three amino acids</scene> 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 ARBs contain a [https://en.wikipedia.org/wiki/Tetrazole tetrazole] group. Studies showed that tetrazole plays an important role in the binding with AT1R.

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@@ Line 26: / Line 26: @@
 === Primary and secondary structure ===
-The human AT1 receptor consists of a 376 amino acid string <ref> [http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?pdbcode=4zud&template=main.html Protein Database (PDBsum): 4zud. European Bioinformatics (EBI); 2013.]</ref>. The protein is composed of
+The human AT1 receptor consists of a 376 amino acid string <ref> [http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?pdbcode=4zud&template=main.html Protein Database (PDBsum): 4zud. European Bioinformatics (EBI); 2013.]</ref>. The protein is composed of <scene name='82/829348/Helix_a/1'>18 α helixes</scene> and a <scene name='82/829348/B_sheet/1'>single β sheet</scene> composed of 3 β strands. Moreover, 7 α helixes are made of a majority of hydrophobic amino acids. These helixes are long enough to cross the membrane and create a <scene name='82/829348/Transmambrane_protein/1'>hydrophobic domain</scene> which is situated into the membrane. The human angiotensin receptor is therefore an α helical trans-membrane protein.
-<scene name='82/829348/Helix_a/1'>18 α helix</scene>
-and <scene name='82/829348/B_sheet/1'>3 β sheets</scene>. Moreover, 7 α helixes are made of a majority of hydrophobic amino acids. These helixes are long enough to cross the membrane and create a <scene name='82/829348/Transmambrane_protein/1'>hydrophobic domain</scene> which is situated into the membrane. The human angiotensin receptor is therefore an α helical trans-membrane protein.
 Since the angiotensin receptor belongs to the GPCRs family, those 7 α helixes contain 3 extracellular and 3 intracellular loops. The N terminus corresponds to the extracellular domain. The C terminal domain is located intracellularly.
 === Ligand binding pocket ===
-In the extracellular environment, there is a β-hairpin in conjugation with <scene name='82/829348/Disulfuric_bridge/2'>two extracellular disulfure bridges</scene>. This structure is responsible for the opening and the locking of the ligand binding pocket <ref> PMID: 23386604  </ref>. The ligand goes into a <scene name='82/829348/Ligand_blinding_pocket/1'>hydrophilic pocket</scene> created into the membrane thanks to the 7 α helix which creates a gate between the membrane and the extracellular environment.
+In the extracellular environment, there is a β-hairpin in conjugation with <scene name='82/829348/Disulfuric_bridge/4'>two extracellular disulfure bridges</scene>. This structure is responsible for the opening and the locking of the ligand binding pocket <ref> PMID: 23386604  </ref>. The ligand goes into a <scene name='82/829348/Ligand_blinding_pocket/1'>hydrophilic pocket</scene> created into the membrane thanks to the 7 α helixes which creates a gate between the membrane and the extracellular environment.
 === G protein-binding site ===
-When the angiotensin II binds to the angiotensin receptor in the ligand binding pocket, the conformation of the trans-membrane domain changes to create a cytosolic cleft for the binding and activation of G proteins. In this cleft, several conserved residues can be found, which form functional motifs present in all [[GPCRs]] <ref> PMID:30608150 </ref>.
+When the angiotensin II binds to the angiotensin receptor in the ligand binding pocket, the conformation of the trans-membrane domain changes to create a cytosolic cleft for the binding and activation of G proteins. In this cleft, several conserved residues can be found, which form functional motifs present in all [[GPCRs]] <ref name='Singh2019'> PMID:30608150 </ref>.
-AngII mediates AT1 receptor activation via stacking interactions between Phe8(AngII)/<scene name='82/829348/His_256/2'>His256</scene>(AT1 receptor) and Tyr4(AngII)/<scene name='82/829348/Asn_111/1'>Asn111</scene>(AT1 receptor). This phenomenon results in a conformational change in transmembrane (TM)3-TM6 helixes and in interaction between TM2 and TM7.
+AngII mediates AT1 receptor activation via stacking interactions between Phe8(AngII)/<scene name='82/829348/His_256/2'>His256</scene>(AT1 receptor) and Tyr4(AngII)/<scene name='82/829348/Asn_111/1'>Asn111</scene>(AT1 receptor). This phenomenon results in a conformational change in transmembrane (TM)3-TM6 helixes and in interaction between TM2 and TM7  <ref name='Singh2019'/>.
 === Interaction with drugs ===
 Angiotensin Receptor Blockers (ARBs) are used to cure diseases linked to AT1R.
-The ARB [https://en.wikipedia.org/wiki/Olmesartan olmesartan] is anchored to ATR1 by the residues <scene name='82/829348/Tyr35/6'>Tyr35</scene>, <scene name='82/829348/Trp84/4'>Trp84</scene> and <scene name='82/829348/Arg167/3'>Arg167</scene>.
+The ARB [https://en.wikipedia.org/wiki/Olmesartan olmesartan] is anchored to ATR1 by the residues <scene name='82/829348/Tyr35/6'>Tyr35</scene>, <scene name='82/829348/Trp84/5'>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"/>.
+<scene name='82/829348/3_residues_bound_to_ligand/2'>Those three amino acids</scene> 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 ARBs contain a [https://en.wikipedia.org/wiki/Tetrazole tetrazole] group. Studies showed that tetrazole plays an important role in the binding with AT1R.