Prinivil/Sandbox 1 - Revision history

Robert Sherman at 00:43, 6 December 2016

2016-12-06T00:43:14Z

←Older revision		Revision as of 00:43, 6 December 2016
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	== Function ==		== Function ==

-	[[Image:LPR_mechanism.png\|thumb\|left\|310×228px\|link=http://proteopedia.org/wiki/images/a/af/LPR_mechanism.png\|Figure 1]] <scene name='74/745974/Bradykinin/1'>Bradykinin</scene> is a common vasodilator that, when bound to ACE, will allow ACE the cleave angiotensin I to angiotensin II, but when bound to lisinopril through competitive inhibition, 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]] <scene name='74/745974/Bradykinin/1'>Bradykinin</scene> is a common vasodilator that, when bound to ACE, will allow ACE the cleave angiotensin I to angiotensin II, but when bound to lisinopril through competitive inhibition, 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.<ref>Brown, N. Vaughan, D. Angiotensin-Converting Enzyme Inhibitors. Circulation. 1998;97:1411-1420. doi: http://dx.doi.org/10.1161/01.CIR.97.14.1411</ref>


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	== Structure and Mechanism ==		== Structure and Mechanism ==

-	[[Image:Prinivil_Bradykinin_binding_sites.png\|thumb\|right\|Figure 2. Lisinopril binding locations]]Lisinopril (prinivil) acts upon the membrane protein by forming tight and nonspecific contacts with the conserved residues in the <scene name='74/745974/Lisinopril_s2_interaction/1'>S2'</scene>, <scene name='74/745974/Lisinopril_s1_interaction/1'>S1'</scene>, and <scene name='74/745974/Lisinopril_s1_1_interaction/1'>S1</scene> positions of the <scene name='74/745974/Lisinopril_ace_complex/2'>ACE</scene>, which is viewed by using JSmol<ref>DOI 10.1002/ijch.201300024</ref> and Jmol.<ref>PMID:21638687</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> The ACE Active site has a NH3+ group which binds to the COOH terminus of the drug. NH of the enzyme binds to the middle C=O group of the drug. The benzene ring of the drug fits into a hydrophobic pocket(S1) of the enzyme. The 5-membered nitrogenous ring of the drug fits to the S2’ pocket. The lysine segment fits into the S1’ pocket, as seen in Figure 2.<ref>Brew, K. Structure of human ACE gives new insights into inhibitor binding and design. TRENDS in Pharm. Sci. 2003 Aug; 24: 8. doi: 10.1016/S0165-6147(03)00199-8</ref> All other ACE inhibitors, such as Captopril, Fentiapril, Pivalopril, etc all have the same general substituents of a phenyl in the S1, lysine in the S1', and proline in the S2' pocket as well as a carboxyl group that binds with a Zn<sup>2+</sup> ion.	+	[[Image:Prinivil_Bradykinin_binding_sites.png\|thumb\|right\|Figure 2. Lisinopril binding locations]]Lisinopril (prinivil) acts upon the membrane protein by forming tight and nonspecific contacts with the conserved residues in the <scene name='74/745974/Lisinopril_s2_interaction/1'>S2'</scene>, <scene name='74/745974/Lisinopril_s1_interaction/1'>S1'</scene>, and <scene name='74/745974/Lisinopril_s1_1_interaction/1'>S1</scene> positions of the <scene name='74/745974/Lisinopril_ace_complex/2'>ACE</scene>, which is viewed by using JSmol<ref>DOI 10.1002/ijch.201300024</ref> and Jmol.<ref>PMID:21638687</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> The ACE Active site has a NH3+ group which binds to the COOH terminus of the drug. NH of the enzyme binds to the middle C=O group of the drug. The benzene ring of the drug fits into a hydrophobic pocket(S1) of the enzyme. The 5-membered nitrogenous ring of the drug fits to the S2’ pocket. The lysine segment fits into the S1’ pocket, as seen in Figure 2.<ref>Brew, K. Structure of human ACE gives new insights into inhibitor binding and design. TRENDS in Pharm. Sci. 2003 Aug; 24: 8. doi: http://dx.doi.org/10.1016/S0165-6147(03)00199-8</ref> All other ACE inhibitors, such as Captopril, Fentiapril, Pivalopril, etc all have the same general substituents of a phenyl in the S1, lysine in the S1', and proline in the S2' pocket as well as a carboxyl group that binds with a Zn<sup>2+</sup> ion.

Robert Sherman at 00:37, 6 December 2016

2016-12-06T00:37:43Z

←Older revision		Revision as of 00:37, 6 December 2016
Line 7:		Line 7:
	== Function ==		== Function ==

-	[[Image:LPR_mechanism.png\|thumb\|left\|310×228px\|link=http://proteopedia.org/wiki/images/a/af/LPR_mechanism.png\|Figure 1]] <scene name='74/745974/Bradykinin/1'>Bradykinin</scene> 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]] <scene name='74/745974/Bradykinin/1'>Bradykinin</scene> is a common vasodilator that, when bound to ACE, will allow ACE the cleave angiotensin I to angiotensin II, but when bound to lisinopril through competitive inhibition, 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.

-	To-do:<br/>
-	- other common and relevant ACE inhibitor drugs<br/>
-	- What are diseases in humans that can be helped by lisinopril or affect lisinopril inhibition efficiency.<br/>
-	- More detail on mechanism. Needs more
-	- Figure out how to use wiki markup in captions of thumbnails if possible (?)




-	== Structure ==

-	[[Image:Prinivil_Bradykinin_binding_sites.png\|thumb\|right\|Lisinopril/Bradykinin binding locations]]Lisinopril (prinivil) acts upon the membrane protein by forming tight and nonspecific contacts with the conserved residues in the <scene name='74/745974/Lisinopril_s2_interaction/1'>S2'</scene>, <scene name='74/745974/Lisinopril_s1_interaction/1'>S1'</scene>, and <scene name='74/745974/Lisinopril_s1_1_interaction/1'>S1</scene> positions of the <scene name='74/745974/Lisinopril_ace_complex/2'>ACE</scene>, which is viewed by using JSmol<ref>DOI 10.1002/ijch.201300024</ref> and Jmol.<ref>PMID:21638687</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>

-	To-do:<br/>
-	- General Information on mass, conformations, stereochemistry, etc.<br/>
-	- Common source of Zn in ACE<br/>
-	- Include Green links for structure viewing of various ACE sites and relevant molecules<br/>
-	- Create structures for viewing

		+	== Structure and Mechanism ==

-		+	[[Image:Prinivil_Bradykinin_binding_sites.png\|thumb\|right\|Figure 2. Lisinopril binding locations]]Lisinopril (prinivil) acts upon the membrane protein by forming tight and nonspecific contacts with the conserved residues in the <scene name='74/745974/Lisinopril_s2_interaction/1'>S2'</scene>, <scene name='74/745974/Lisinopril_s1_interaction/1'>S1'</scene>, and <scene name='74/745974/Lisinopril_s1_1_interaction/1'>S1</scene> positions of the <scene name='74/745974/Lisinopril_ace_complex/2'>ACE</scene>, which is viewed by using JSmol<ref>DOI 10.1002/ijch.201300024</ref> and Jmol.<ref>PMID:21638687</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> The ACE Active site has a NH3+ group which binds to the COOH terminus of the drug. NH of the enzyme binds to the middle C=O group of the drug. The benzene ring of the drug fits into a hydrophobic pocket(S1) of the enzyme. The 5-membered nitrogenous ring of the drug fits to the S2’ pocket. The lysine segment fits into the S1’ pocket, as seen in Figure 2.<ref>Brew, K. Structure of human ACE gives new insights into inhibitor binding and design. TRENDS in Pharm. Sci. 2003 Aug; 24: 8. doi: 10.1016/S0165-6147(03)00199-8</ref> All other ACE inhibitors, such as Captopril, Fentiapril, Pivalopril, etc all have the same general substituents of a phenyl in the S1, lysine in the S1', and proline in the S2' pocket as well as a carboxyl group that binds with a Zn<sup>2+</sup> ion.
-		+
-		+
-		+
-		+
-		+
-	== ~~Mechanism~~ ==	+
-		+
-	ACE Active site has a NH3+ group which binds to the COOH terminus of the drug. NH of the enzyme binds to the middle C=O group of the drug. The benzene ring of the drug fits into a hydrophobic pocket(S1) of the enzyme. The 5-membered nitrogenous ring of the drug fits to the S2’ pocket. The lysine segment fits into the S1’ pocket.	+
-		+
-	~~To-do~~:	+
-		+
-	- all ~~relevant~~, ~~interacting residues described~~<~~br/~~>	+
-	~~- known mechanistic theories~~<br/>	+
-	~~- Figure out how to make multiple footnotes referencing the same paper~~.	+
-		+

Robert Sherman at 23:54, 5 December 2016

2016-12-05T23:54:47Z

←Older revision		Revision as of 23:54, 5 December 2016
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	== Structure ==		== Structure ==

-	[[Image:~~LPR Binding~~.png\|thumb\|right\|Lisinopril binding locations]]Lisinopril (prinivil) acts upon the membrane protein by forming tight and nonspecific contacts with the conserved residues in the <scene name='74/745974/Lisinopril_s2_interaction/1'>S2'</scene>, <scene name='74/745974/Lisinopril_s1_interaction/1'>S1'</scene>, and <scene name='74/745974/Lisinopril_s1_1_interaction/1'>S1</scene> positions of the <scene name='74/745974/Lisinopril_ace_complex/2'>ACE</scene>, which is viewed by using JSmol<ref>DOI 10.1002/ijch.201300024</ref> and Jmol.<ref>PMID:21638687</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>	+	[[Image:Prinivil_Bradykinin_binding_sites.png\|thumb\|right\|Lisinopril/Bradykinin binding locations]]Lisinopril (prinivil) acts upon the membrane protein by forming tight and nonspecific contacts with the conserved residues in the <scene name='74/745974/Lisinopril_s2_interaction/1'>S2'</scene>, <scene name='74/745974/Lisinopril_s1_interaction/1'>S1'</scene>, and <scene name='74/745974/Lisinopril_s1_1_interaction/1'>S1</scene> positions of the <scene name='74/745974/Lisinopril_ace_complex/2'>ACE</scene>, which is viewed by using JSmol<ref>DOI 10.1002/ijch.201300024</ref> and Jmol.<ref>PMID:21638687</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>

	To-do:<br/>		To-do:<br/>
Line 27:		Line 27:
	- Include Green links for structure viewing of various ACE sites and relevant molecules<br/>		- Include Green links for structure viewing of various ACE sites and relevant molecules<br/>
	- Create structures for viewing		- Create structures for viewing
		+
		+
		+
		+

Robert Sherman at 23:38, 5 December 2016

2016-12-05T23:38:15Z

←Older revision		Revision as of 23:38, 5 December 2016
Line 1:		Line 1:
	==Lisinopril==		==Lisinopril==
	<StructureSection load="" size="340" frame="true" spin="on" scene="74/745974/Lisinopril_stickandball/3" align="right"/>		<StructureSection load="" size="340" frame="true" spin="on" scene="74/745974/Lisinopril_stickandball/3" align="right"/>
-
-	'''TEMP'''=Green links for structure<br/>
-	''TEMP''=Needs Editing

	<scene name='74/745974/Lisinopril_2/1'>Lisinopril</scene><ref>Canner, D. Lisinopril http://proteopedia.org/wiki/index.php/prinivil (accessed Nov 10, 2016).</ref> 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> Lisinopril functions as a competitive inhibitor of the angiotensin converting enzyme (ACE). <scene name='74/745974/Lisinopril_ace_complex/4'>ACE</scene><ref>DOI 10.1016/j.jmb.2010.05.024</ref> cleaves specific residues of an inactive <scene name='74/745974/Angiotensin_i/4'>angiotensin 1</scene> near the C domain (domain closer to the C-terminus) to form a potent vasopressor octapeptide known as <scene name='74/745974/Angiotensin_ii/2'>angiotensin 2</scene>; 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 by interacting through hydrogen bonding along with an ionic binding of a <scene name='74/745974/Lisinopril_ace_complex_label/6'>Zinc</scene> atom and the carboxylate group which configures the molecule in 3D space.		<scene name='74/745974/Lisinopril_2/1'>Lisinopril</scene><ref>Canner, D. Lisinopril http://proteopedia.org/wiki/index.php/prinivil (accessed Nov 10, 2016).</ref> 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> Lisinopril functions as a competitive inhibitor of the angiotensin converting enzyme (ACE). <scene name='74/745974/Lisinopril_ace_complex/4'>ACE</scene><ref>DOI 10.1016/j.jmb.2010.05.024</ref> cleaves specific residues of an inactive <scene name='74/745974/Angiotensin_i/4'>angiotensin 1</scene> near the C domain (domain closer to the C-terminus) to form a potent vasopressor octapeptide known as <scene name='74/745974/Angiotensin_ii/2'>angiotensin 2</scene>; 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 by interacting through hydrogen bonding along with an ionic binding of a <scene name='74/745974/Lisinopril_ace_complex_label/6'>Zinc</scene> atom and the carboxylate group which configures the molecule in 3D space.

-	To-do:<br/>
-	- Make sure everything is well-defined and linked for easy understanding.

	== Function ==		== Function ==

Robert Sherman at 02:48, 5 December 2016

2016-12-05T02:48:35Z

←Older revision		Revision as of 02:48, 5 December 2016
Line 25:		Line 25:
	== Structure ==		== Structure ==

-	[[Image:LPR Binding.png\|thumb\|right\|Lisinopril binding locations]]Lisinopril (prinivil) acts upon the membrane protein by forming tight and nonspecific contacts with the conserved residues in the <scene name='74/745974/Lisinopril_s2_interaction/1'>S2'</scene>, <scene name='74/745974/Lisinopril_s1_interaction/1'>S1'</scene>, and <scene name='74/745974/Lisinopril_s1_1_interaction/1'>S1</scene> positions of the <scene name='74/745974/Lisinopril_ace_complex/2'>ACE</scene>, which is viewed by using JSmol<ref>DOI 10.1002/ijch.201300024</ref> and Jmol.<ref>PMID:21638687</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>	+	[[Image:LPR Binding.png\|thumb\|right\|Lisinopril binding locations]]Lisinopril (prinivil) acts upon the membrane protein by forming tight and nonspecific contacts with the conserved residues in the <scene name='74/745974/Lisinopril_s2_interaction/1'>S2'</scene>, <scene name='74/745974/Lisinopril_s1_interaction/1'>S1'</scene>, and <scene name='74/745974/Lisinopril_s1_1_interaction/1'>S1</scene> positions of the <scene name='74/745974/Lisinopril_ace_complex/2'>ACE</scene>, which is viewed by using JSmol<ref>DOI 10.1002/ijch.201300024</ref> and Jmol.<ref>PMID:21638687</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>

	To-do:<br/>		To-do:<br/>

Robert Sherman at 00:49, 5 December 2016

2016-12-05T00:49:03Z

←Older revision		Revision as of 00:49, 5 December 2016
Line 25:		Line 25:
	== Structure ==		== Structure ==

-	[[Image:LPR Binding.png\|thumb\|right\|Lisinopril binding locations]]Lisinopril (prinivil) acts upon the membrane protein by forming tight and nonspecific contacts with the conserved residues in the <scene name='74/745974/Lisinopril_s2_interaction/1'>S2'</scene>, <scene name='74/745974/Lisinopril_s1_interaction/1'>S1'</scene>, and '''S1~~'''~~ positions of the <scene name='74/745974/Lisinopril_ace_complex/2'>ACE</scene>, which is viewed by using JSmol<ref>DOI 10.1002/ijch.201300024</ref> and Jmol.<ref>PMID:21638687</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>	+	[[Image:LPR Binding.png\|thumb\|right\|Lisinopril binding locations]]Lisinopril (prinivil) acts upon the membrane protein by forming tight and nonspecific contacts with the conserved residues in the <scene name='74/745974/Lisinopril_s2_interaction/1'>S2'</scene>, <scene name='74/745974/Lisinopril_s1_interaction/1'>S1'</scene>, and <scene name='74/745974/Lisinopril_s1_1_interaction/1'>S1</scene> positions of the <scene name='74/745974/Lisinopril_ace_complex/2'>ACE</scene>, which is viewed by using JSmol<ref>DOI 10.1002/ijch.201300024</ref> and Jmol.<ref>PMID:21638687</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>

	To-do:<br/>		To-do:<br/>

Robert Sherman at 00:36, 5 December 2016

2016-12-05T00:36:38Z

←Older revision		Revision as of 00:36, 5 December 2016
Line 25:		Line 25:
	== Structure ==		== Structure ==

-	[[Image:LPR Binding.png\|thumb\|right\|Lisinopril binding locations]]Lisinopril (prinivil) acts upon the membrane protein by forming tight and nonspecific contacts with the conserved residues in the <scene name='74/745974/Lisinopril_s2_interaction/1'>S2'</scene>, '''~~S1’~~,~~'''~~ and '''S1''' positions of the <scene name='74/745974/Lisinopril_ace_complex/2'>ACE</scene>, which is viewed by using JSmol<ref>DOI 10.1002/ijch.201300024</ref> and Jmol.<ref>PMID:21638687</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>	+	[[Image:LPR Binding.png\|thumb\|right\|Lisinopril binding locations]]Lisinopril (prinivil) acts upon the membrane protein by forming tight and nonspecific contacts with the conserved residues in the <scene name='74/745974/Lisinopril_s2_interaction/1'>S2'</scene>, <scene name='74/745974/Lisinopril_s1_interaction/1'>S1'</scene>, and '''S1''' positions of the <scene name='74/745974/Lisinopril_ace_complex/2'>ACE</scene>, which is viewed by using JSmol<ref>DOI 10.1002/ijch.201300024</ref> and Jmol.<ref>PMID:21638687</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>

	To-do:<br/>		To-do:<br/>

Robert Sherman at 00:12, 5 December 2016

2016-12-05T00:12:36Z

←Older revision		Revision as of 00:12, 5 December 2016
Line 25:		Line 25:
	== Structure ==		== Structure ==

-	[[Image:LPR Binding.png\|thumb\|right\|Lisinopril binding locations]]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>, which is viewed by using JSmol<ref>DOI 10.1002/ijch.201300024</ref> and Jmol.<ref>PMID:21638687</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>	+	[[Image:LPR Binding.png\|thumb\|right\|Lisinopril binding locations]]Lisinopril (prinivil) acts upon the membrane protein by forming tight and nonspecific contacts with the conserved residues in the <scene name='74/745974/Lisinopril_s2_interaction/1'>S2'</scene>, '''S1’,''' and '''S1''' positions of the <scene name='74/745974/Lisinopril_ace_complex/2'>ACE</scene>, which is viewed by using JSmol<ref>DOI 10.1002/ijch.201300024</ref> and Jmol.<ref>PMID:21638687</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>

	To-do:<br/>		To-do:<br/>

Robert Sherman at 23:25, 4 December 2016

2016-12-04T23:25:53Z

←Older revision		Revision as of 23:25, 4 December 2016
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	''TEMP''=Needs Editing		''TEMP''=Needs Editing

-	<scene name='74/745974/Lisinopril_2/1'>Lisinopril</scene><ref>Canner, D. Lisinopril http://proteopedia.org/wiki/index.php/prinivil (accessed Nov 10, 2016).</ref> 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> Lisinopril functions as a competitive inhibitor of the angiotensin converting enzyme (ACE). <scene name='74/745974/Lisinopril_ace_complex/4'>ACE</scene><ref>DOI 10.1016/j.jmb.2010.05.024</ref> cleaves specific residues of an inactive <scene name='74/745974/Angiotensin_i/4'>angiotensin 1</scene> near the C domain (domain closer to the C-terminus) to form a potent vasopressor octapeptide known as <scene name='74/745974/Angiotensin_ii/2'>angiotensin 2</scene>; 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 <scene name='74/745974/Lisinopril_ace_complex_label/6'>Zinc</scene> atom and the carboxylate group which configures the molecule in 3D space.	+	<scene name='74/745974/Lisinopril_2/1'>Lisinopril</scene><ref>Canner, D. Lisinopril http://proteopedia.org/wiki/index.php/prinivil (accessed Nov 10, 2016).</ref> 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> Lisinopril functions as a competitive inhibitor of the angiotensin converting enzyme (ACE). <scene name='74/745974/Lisinopril_ace_complex/4'>ACE</scene><ref>DOI 10.1016/j.jmb.2010.05.024</ref> cleaves specific residues of an inactive <scene name='74/745974/Angiotensin_i/4'>angiotensin 1</scene> near the C domain (domain closer to the C-terminus) to form a potent vasopressor octapeptide known as <scene name='74/745974/Angiotensin_ii/2'>angiotensin 2</scene>; 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 by interacting through hydrogen bonding along with an ionic binding of a <scene name='74/745974/Lisinopril_ace_complex_label/6'>Zinc</scene> atom and the carboxylate group which configures the molecule in 3D space.

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Robert Sherman at 22:59, 4 December 2016

2016-12-04T22:59:19Z

←Older revision		Revision as of 22:59, 4 December 2016
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-	<scene name='74/745974/~~Lisinopril_stickandball~~/3'>Lisinopril</scene><ref>Canner, D. Lisinopril http://proteopedia.org/wiki/index.php/prinivil (accessed Nov 10, 2016).</ref> 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> Lisinopril functions as a competitive inhibitor of the angiotensin converting enzyme (ACE). <scene name='74/745974/Lisinopril_ace_complex/4'>ACE</scene><ref>DOI 10.1016/j.jmb.2010.05.024</ref> cleaves specific residues of an inactive <scene name='74/745974/Angiotensin_i/4'>angiotensin 1</scene> near the C domain (domain closer to the C-terminus) to form a potent vasopressor octapeptide known as <scene name='74/745974/Angiotensin_ii/2'>angiotensin 2</scene>; 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 <scene name='74/745974/Lisinopril_ace_complex_label/6'>Zinc</scene> atom and the carboxylate group which configures the molecule in 3D space.	+	<scene name='74/745974/Lisinopril_2/1'>Lisinopril</scene><ref>Canner, D. Lisinopril http://proteopedia.org/wiki/index.php/prinivil (accessed Nov 10, 2016).</ref> 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> Lisinopril functions as a competitive inhibitor of the angiotensin converting enzyme (ACE). <scene name='74/745974/Lisinopril_ace_complex/4'>ACE</scene><ref>DOI 10.1016/j.jmb.2010.05.024</ref> cleaves specific residues of an inactive <scene name='74/745974/Angiotensin_i/4'>angiotensin 1</scene> near the C domain (domain closer to the C-terminus) to form a potent vasopressor octapeptide known as <scene name='74/745974/Angiotensin_ii/2'>angiotensin 2</scene>; 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 <scene name='74/745974/Lisinopril_ace_complex_label/6'>Zinc</scene> atom and the carboxylate group which configures the molecule in 3D space.

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