Prinivil/Sandbox 1: Difference between revisions

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''TEMP''=Needs Editing

'''Lisinopril''' (Commercially known as Prinivil) functions as a competitive inhibitor of the angiotensin converting enzyme (ACE). '''ACE''' cleaves specific residues of an inactive '''angiotensin 1''' near the C domain (domain closer to the C-terminus) to form a potent vasopressor octapeptide known as '''angiotensin 2'''; however the specific substrate binding and catalysis is not fully understood. ACE is found as a type 1 membrane bound dipeptidyl carboxypeptidase that regulates blood pressure and steady state equilibrium of ions within the blood. Located on vascular epithelial cells, the drug interaction takes place on the surface of the cell within an artery/vein.<ref>DOI 10.1038/nature01370</ref> Lisinopril (prinivil) acts upon the membrane protein by forming tight and nonspecific contacts with the conserved residues in the '''S2’,''' '''S1’,''' and '''S1''' positions of the ACE. The ligand is stabilized by ''3 residues (2 histidines (RES #) and 1 glutamic acid (RES #))'' ''We need to add the specific residue bindings here at some point'' interacting through hydrogen bonding along with an ionic binding of a '''Zinc''' atom and the carboxylate group which configures the molecule in 3D space.

'''Lisinopril''' (Commercially known as Prinivil) functions as a competitive inhibitor of the angiotensin converting enzyme (ACE). '''ACE''' cleaves specific residues of an inactive '''angiotensin 1''' near the C domain (domain closer to the C-terminus) to form a potent vasopressor octapeptide known as '''angiotensin 2'''; however the specific substrate binding and catalysis is not fully understood. ACE is found as a type 1 membrane bound dipeptidyl carboxypeptidase that regulates blood pressure and steady state equilibrium of ions within the blood.

== Drug Function ==

[[Image:LPR_mechanism.png|left|~~thumb~~|Figure 1]]As seen in Figure 1, bradykinin will bind to the ACE, which allows for the conversion of angiotensin I to ~~angiotensis~~ II by ~~theACE~~/bradykinin complex. By blocking the active site of ACE, an inactive ~~angiostensin~~ 1 cannot be cleaved, which would block the cascade of events triggered by angiotensin 2 binding to type 1 AT2 receptor to create vasoconstriction. ACE is also able to deactivate a common vasodilator known as '''bradykinin''', but when bound to lisinopril, bradykinin levels rise in the blood stream causing a decrease in blood pressure and increased vasodilation.

[[Image:LPR_mechanism.png|thumb|left|310×228px|link=http://proteopedia.org/wiki/images/a/af/LPR_mechanism.png|Figure 1]]Bradykinin is a common vasodilator that, when bound to ACE, will allow ACE the cleave angiotensin I to angiotensin II, but when bound to lisinopril, bradykinin levels rise in the blood stream causing a decrease in blood pressure and increased vasodilation. As seen in Figure 1, bradykinin will bind to the ACE, which allows for the conversion of angiotensin I to angiotensin II by the ACE/bradykinin complex. By blocking the active site of ACE, an inactive angiotensin 1 cannot be cleaved, which would block the cascade of events triggered by angiotensin 2 binding to type 1 AT2 receptor to create vasoconstriction.

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== Structure ==

<scene name='74/745974/Lisinopril_ace_complex/2'>~~Lisinopril/~~ACE ~~Complex~~</scene><ref>DOI 10.1016/j.jmb.2010.05.024</ref>

Located on vascular epithelial cells, the drug interaction takes place on the surface of the cell within an artery/vein.<ref>DOI 10.1038/nature01370</ref> Lisinopril (prinivil) acts upon the membrane protein by forming tight and nonspecific contacts with the conserved residues in the '''S2’,''' '''S1’,''' and '''S1''' positions of the <scene name='74/745974/Lisinopril_ace_complex/2'>ACE</scene><ref>DOI 10.1016/j.jmb.2010.05.024</ref>. The ligand is stabilized by ''3 residues (2 histidines (RES #) and 1 glutamic acid (RES #))'' ''We need to add the specific residue bindings here at some point'' interacting through hydrogen bonding along with an ionic binding of a '''Zinc''' atom and the carboxylate group which configures the molecule in 3D space.

== Mechanism ==

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@@ Line 5: / Line 5: @@
 ''TEMP''=Needs Editing
-'''Lisinopril''' (Commercially known as Prinivil) functions as a competitive inhibitor of the angiotensin converting enzyme (ACE). '''ACE''' cleaves specific residues of an inactive '''angiotensin 1''' near the C domain (domain closer to the C-terminus) to form a potent vasopressor octapeptide known as '''angiotensin 2'''; however the specific substrate binding and catalysis is not fully understood. ACE is found as a type 1 membrane bound dipeptidyl carboxypeptidase that regulates blood pressure and steady state equilibrium of ions within the blood. Located on vascular epithelial cells, the drug interaction takes place on the surface of the cell within an artery/vein.<ref>DOI 10.1038/nature01370</ref> Lisinopril (prinivil) acts upon the membrane protein by forming tight and nonspecific contacts with the conserved residues in the '''S2’,''' '''S1’,''' and '''S1''' positions of the ACE. The ligand is stabilized by ''3 residues (2 histidines (RES #) and 1 glutamic acid (RES #))'' ''We need to add the specific residue bindings here at some point'' interacting through hydrogen bonding along with an ionic binding of a '''Zinc''' atom and the carboxylate group which configures the molecule in 3D space.
+'''Lisinopril''' (Commercially known as Prinivil) functions as a competitive inhibitor of the angiotensin converting enzyme (ACE). '''ACE''' cleaves specific residues of an inactive '''angiotensin 1''' near the C domain (domain closer to the C-terminus) to form a potent vasopressor octapeptide known as '''angiotensin 2'''; however the specific substrate binding and catalysis is not fully understood. ACE is found as a type 1 membrane bound dipeptidyl carboxypeptidase that regulates blood pressure and steady state equilibrium of ions within the blood.
 == Drug Function ==
-[[Image:LPR_mechanism.png|left|thumb|Figure 1]]As seen in Figure 1, bradykinin will bind to the ACE, which allows for the conversion of angiotensin I to angiotensis II by theACE/bradykinin complex. By blocking the active site of ACE, an inactive angiostensin 1 cannot be cleaved, which would block the cascade of events triggered by angiotensin 2 binding to type 1 AT2 receptor to create vasoconstriction. ACE is also able to deactivate a common vasodilator known as '''bradykinin''', but when bound to lisinopril, bradykinin levels rise in the blood stream causing a decrease in blood pressure and increased vasodilation.
+[[Image:LPR_mechanism.png|thumb|left|310×228px|link=http://proteopedia.org/wiki/images/a/af/LPR_mechanism.png|Figure 1]]Bradykinin is a common vasodilator that, when bound to ACE, will allow ACE the cleave angiotensin I to angiotensin II, but when bound to lisinopril, bradykinin levels rise in the blood stream causing a decrease in blood pressure and increased vasodilation. As seen in Figure 1, bradykinin will bind to the ACE, which allows for the conversion of angiotensin I to angiotensin II by the ACE/bradykinin complex. By blocking the active site of ACE, an inactive angiotensin 1 cannot be cleaved, which would block the cascade of events triggered by angiotensin 2 binding to type 1 AT2 receptor to create vasoconstriction.
@@ Line 17: / Line 18: @@
 == Structure ==
-<scene name='74/745974/Lisinopril_ace_complex/2'>Lisinopril/ACE Complex</scene><ref>DOI 10.1016/j.jmb.2010.05.024</ref>
+Located on vascular epithelial cells, the drug interaction takes place on the surface of the cell within an artery/vein.<ref>DOI 10.1038/nature01370</ref> Lisinopril (prinivil) acts upon the membrane protein by forming tight and nonspecific contacts with the conserved residues in the '''S2’,''' '''S1’,''' and '''S1''' positions of the <scene name='74/745974/Lisinopril_ace_complex/2'>ACE</scene><ref>DOI 10.1016/j.jmb.2010.05.024</ref>. The ligand is stabilized by ''3 residues (2 histidines (RES #) and 1 glutamic acid (RES #))'' ''We need to add the specific residue bindings here at some point'' interacting through hydrogen bonding along with an ionic binding of a '''Zinc''' atom and the carboxylate group which configures the molecule in 3D space.
 == Mechanism ==