Prinivil/Sandbox 1: Difference between revisions
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<ref>Canner, D. Lisinopril http://proteopedia.org/wiki/index.php/prinivil (accessed Nov 10, 2016).</ref>'''Lisinopril''' ( | <ref>Canner, D. Lisinopril http://proteopedia.org/wiki/index.php/prinivil (accessed Nov 10, 2016).</ref>'''Lisinopril''' was patented by Merck & Co. under the brand name of Prinivil.<ref>PRINIVIL® (lisinopril) https://www.merck.com/product/usa/pi_circulars/p/prinivil/prinivil_pi.pdf (accessed Nov 16, 2016).</ref> functions as a competitive inhibitor of the angiotensin converting enzyme (ACE). Lisinopril was patented '''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>. 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. | ||
== Drug Function == | == Drug Function == | ||
[[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. | [[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 == | == Structure == | ||
[[Image:LPR Binding.png|thumb|right]]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 <scenename='74/745974/Lisinopril_ace_complex/2'>ACE</scene><ref>DOI 10.1016/j.jmb.2010.05.024</ref>. The S1’ subsite contains '''Glu162''' residue that interacts strongly with the lysine residue of lisinopril, the S1 subsite is surrounded with hydrophobic residues '''Phe512''' and '''Val518''', and the S2’ subsite contains '''Lys511''' and '''Tyr520''' to form strong hydrogen bonds with the C-terminus proline of lisinopril.<ref>DOI 10.1021/ci200083f</ref> | |||
== Mechanism of Action == | |||
