6i3i - Revision history

OCA at 11:45, 24 January 2024

OCA — Wed, 24 Jan 2024 11:45:36 GMT

←Older revision		Revision as of 11:45, 24 January 2024
Line 1:		Line 1:

	==Crystal structure of reactive center loop (RCL) cleaved angiotensinogen==		==Crystal structure of reactive center loop (RCL) cleaved angiotensinogen==
-	<StructureSection load='6i3i' size='340' side='right' caption='[[6i3i]], [[Resolution\|resolution]] 2.97Å' scene=''>	+	<StructureSection load='6i3i' size='340' side='right'caption='[[6i3i]], [[Resolution\|resolution]] 2.97Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6i3i]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I3I OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6I3I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6i3i]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I3I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6I3I FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=NAG:N~~-~~ACETYL-D-GLUCOSAMINE'>NAG</scene>~~</td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.97Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~AGT, SERPINA8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode~~=~~Info&srchmode~~=~~5&id=9606 HUMAN])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6i3i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i3i OCA], [~~http~~://pdbe.org/6i3i PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6i3i RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6i3i PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6i3i ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6i3i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i3i OCA], [https://pdbe.org/6i3i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6i3i RCSB], [https://www.ebi.ac.uk/pdbsum/6i3i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6i3i ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/ANGT_HUMAN ANGT_HUMAN]] Genetic variations in AGT are a cause of susceptibility to essential hypertension (EHT) [MIM:[~~http~~://omim.org/entry/145500 145500]]. Essential hypertension is a condition in which blood pressure is consistently higher than normal with no identifiable cause. Defects in AGT are a cause of renal tubular dysgenesis (RTD) [MIM:[~~http~~://omim.org/entry/267430 267430]]. RTD is an autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype).<ref>PMID:16116425</ref>	+	[https://www.uniprot.org/uniprot/ANGT_HUMAN ANGT_HUMAN] Genetic variations in AGT are a cause of susceptibility to essential hypertension (EHT) [MIM:[https://omim.org/entry/145500 145500]. Essential hypertension is a condition in which blood pressure is consistently higher than normal with no identifiable cause. Defects in AGT are a cause of renal tubular dysgenesis (RTD) [MIM:[https://omim.org/entry/267430 267430]. RTD is an autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype).<ref>PMID:16116425</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/ANGT_HUMAN ANGT_HUMAN]] Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis.<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref> Angiotensin-2: acts directly on vascular smooth muscle as a potent vasoconstrictor, affects cardiac contractility and heart rate through its action on the sympathetic nervous system, and alters renal sodium and water absorption through its ability to stimulate the zona glomerulosa cells of the adrenal cortex to synthesize and secrete aldosterone.<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref> Angiotensin-3: stimulates aldosterone release.<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref> Angiotensin 1-7: is a ligand for the G-protein coupled receptor MAS1 (By similarity). Has vasodilator and antidiuretic effects (By similarity). Has an antithrombotic effect that involves MAS1-mediated release of nitric oxide from platelets (By similarity).<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref>	+	[https://www.uniprot.org/uniprot/ANGT_HUMAN ANGT_HUMAN] Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis.<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref> Angiotensin-2: acts directly on vascular smooth muscle as a potent vasoconstrictor, affects cardiac contractility and heart rate through its action on the sympathetic nervous system, and alters renal sodium and water absorption through its ability to stimulate the zona glomerulosa cells of the adrenal cortex to synthesize and secrete aldosterone.<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref> Angiotensin-3: stimulates aldosterone release.<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref> Angiotensin 1-7: is a ligand for the G-protein coupled receptor MAS1 (By similarity). Has vasodilator and antidiuretic effects (By similarity). Has an antithrombotic effect that involves MAS1-mediated release of nitric oxide from platelets (By similarity).<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 6i3i" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6i3i" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Serpin 3D structures\|Serpin 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Read, R J~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Yan, Y~~]]	+	[[Category: Read RJ]]
-	[[Category: ~~Angiotensinogen]]~~	+	[[Category: Yan Y]]
-	~~[[Category: Hormone]]~~	+
-	~~[[Category: Reactive center loop~~]]	+

OCA at 06:23, 2 January 2019

OCA — Wed, 02 Jan 2019 06:23:28 GMT

←Older revision		Revision as of 06:23, 2 January 2019
Line 3:		Line 3:
	<StructureSection load='6i3i' size='340' side='right' caption='[[6i3i]], [[Resolution\|resolution]] 2.97Å' scene=''>		<StructureSection load='6i3i' size='340' side='right' caption='[[6i3i]], [[Resolution\|resolution]] 2.97Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6i3i]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I3I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I3I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6i3i]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I3I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I3I FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AGT, SERPINA8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6i3i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i3i OCA], [http://pdbe.org/6i3i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i3i RCSB], [http://www.ebi.ac.uk/pdbsum/6i3i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i3i ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6i3i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i3i OCA], [http://pdbe.org/6i3i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i3i RCSB], [http://www.ebi.ac.uk/pdbsum/6i3i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i3i ProSAT]</span></td></tr>
	</table>		</table>
Line 11:		Line 12:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/ANGT_HUMAN ANGT_HUMAN]] Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis.<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref> Angiotensin-2: acts directly on vascular smooth muscle as a potent vasoconstrictor, affects cardiac contractility and heart rate through its action on the sympathetic nervous system, and alters renal sodium and water absorption through its ability to stimulate the zona glomerulosa cells of the adrenal cortex to synthesize and secrete aldosterone.<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref> Angiotensin-3: stimulates aldosterone release.<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref> Angiotensin 1-7: is a ligand for the G-protein coupled receptor MAS1 (By similarity). Has vasodilator and antidiuretic effects (By similarity). Has an antithrombotic effect that involves MAS1-mediated release of nitric oxide from platelets (By similarity).<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref>		[[http://www.uniprot.org/uniprot/ANGT_HUMAN ANGT_HUMAN]] Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis.<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref> Angiotensin-2: acts directly on vascular smooth muscle as a potent vasoconstrictor, affects cardiac contractility and heart rate through its action on the sympathetic nervous system, and alters renal sodium and water absorption through its ability to stimulate the zona glomerulosa cells of the adrenal cortex to synthesize and secrete aldosterone.<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref> Angiotensin-3: stimulates aldosterone release.<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref> Angiotensin 1-7: is a ligand for the G-protein coupled receptor MAS1 (By similarity). Has vasodilator and antidiuretic effects (By similarity). Has an antithrombotic effect that involves MAS1-mediated release of nitric oxide from platelets (By similarity).<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The renin-angiotensin cascade is a hormone system that regulates blood pressure and fluid balance. Renin-mediated cleavage of the angiotensin I peptide from the N-terminus of angiotensinogen (AGT) is the rate-limiting step of this cascade; however, the detailed molecular mechanism underlying this step is unclear. Here, we solved the crystal structures of glycosylated human AGT (2.30 A resolution), its encounter complex with renin (2.55 A), AGT cleaved in its reactive center loop (RCL; 2.97 A) and spent AGT from which the N-terminal angiotensin peptide was removed (2.63 A). These structures revealed that AGT undergoes profound conformational changes and binds renin through a tail-into-mouth allosteric mechanism that inserts the N-terminus into a pocket equivalent to a hormone binding site on other serpins. These changes fully extended the N-terminal tail, with the scissile bond for angiotensin release docked in renin's active site. Insertion of the N-terminus into this pocket accompanied a complete unwinding of helix H of AGT, which, in turn, formed key interactions with renin in the complementary binding interface. Mutagenesis and kinetic analyses confirmed that renin-mediated production of angiotensin I is controlled by interactions of amino acid residues and glycan components outside renin's active site cleft. Our findings indicate that AGT adapts unique serpin features for hormone delivery and binds renin through concerted movements in the N-terminal tail and in its main body to modulate angiotensin release. These insights provide a structural basis for the development of agents that attenuate angiotensin release by targeting AGT's hormone binding pocket.
		+
		+	Structural basis for the specificity of renin-mediated angiotensinogen cleavage.,Yan Y, Zhou A, Carrell RW, Read RJ J Biol Chem. 2018 Dec 18. pii: RA118.006608. doi: 10.1074/jbc.RA118.006608. PMID:30563843<ref>PMID:30563843</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6i3i" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Read, R J]]		[[Category: Read, R J]]
	[[Category: Yan, Y]]		[[Category: Yan, Y]]

OCA at 08:24, 26 December 2018

OCA — Wed, 26 Dec 2018 08:24:26 GMT

←Older revision		Revision as of 08:24, 26 December 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6i3i is ~~ON HOLD until Paper Publication~~	+	==Crystal structure of reactive center loop (RCL) cleaved angiotensinogen==
-		+	<StructureSection load='6i3i' size='340' side='right' caption='[[6i3i]], [[Resolution\|resolution]] 2.97Å' scene=''>
-	~~Authors~~: ~~Yan~~, Y., ~~Read~~, R.J.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6i3i]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I3I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I3I FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure~~ of ~~reactive center loop~~ (~~RCL~~) ~~cleaved angiotensinogen~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6i3i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i3i OCA], [http://pdbe.org/6i3i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i3i RCSB], [http://www.ebi.ac.uk/pdbsum/6i3i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i3i ProSAT]</span></td></tr>
-	[[Category: Read, R.J]]	+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/ANGT_HUMAN ANGT_HUMAN]] Genetic variations in AGT are a cause of susceptibility to essential hypertension (EHT) [MIM:[http://omim.org/entry/145500 145500]]. Essential hypertension is a condition in which blood pressure is consistently higher than normal with no identifiable cause. Defects in AGT are a cause of renal tubular dysgenesis (RTD) [MIM:[http://omim.org/entry/267430 267430]]. RTD is an autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype).<ref>PMID:16116425</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ANGT_HUMAN ANGT_HUMAN]] Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis.<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref> Angiotensin-2: acts directly on vascular smooth muscle as a potent vasoconstrictor, affects cardiac contractility and heart rate through its action on the sympathetic nervous system, and alters renal sodium and water absorption through its ability to stimulate the zona glomerulosa cells of the adrenal cortex to synthesize and secrete aldosterone.<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref> Angiotensin-3: stimulates aldosterone release.<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref> Angiotensin 1-7: is a ligand for the G-protein coupled receptor MAS1 (By similarity). Has vasodilator and antidiuretic effects (By similarity). Has an antithrombotic effect that involves MAS1-mediated release of nitric oxide from platelets (By similarity).<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Read, R J]]
	[[Category: Yan, Y]]		[[Category: Yan, Y]]
		+	[[Category: Angiotensinogen]]
		+	[[Category: Hormone]]
		+	[[Category: Reactive center loop]]

OCA: Protected "6i3i" [edit=sysop:move=sysop]

OCA — Wed, 14 Nov 2018 06:21:01 GMT

Protected "6i3i" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:21, 14 November 2018

OCA: New page: '''Unreleased structure''' The entry 6i3i is ON HOLD until Paper Publication Authors: Yan, Y., Read, R.J. Description: Crystal structure of reactive center loop (RCL) cleaved angiotens...

OCA — Wed, 14 Nov 2018 06:20:59 GMT

New page: '''Unreleased structure''' The entry 6i3i is ON HOLD until Paper Publication Authors: Yan, Y., Read, R.J. Description: Crystal structure of reactive center loop (RCL) cleaved angiotens...

New page

'''Unreleased structure'''

The entry 6i3i is ON HOLD until Paper Publication

Authors: Yan, Y., Read, R.J.

Description: Crystal structure of reactive center loop (RCL) cleaved angiotensinogen
[[Category: Unreleased Structures]]
[[Category: Read, R.J]]
[[Category: Yan, Y]]