View source for 2wxw


==Crystal structure of human angiotensinogen==
<StructureSection load='2wxw' size='340' side='right'caption='[[2wxw]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2wxw]] 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=2WXW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WXW FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3&#8491;</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=2wxw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wxw OCA], [https://pdbe.org/2wxw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wxw RCSB], [https://www.ebi.ac.uk/pdbsum/2wxw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wxw ProSAT]</span></td></tr>
</table>
== Disease ==
[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 ==
[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;">
== Publication Abstract from PubMed ==
Blood pressure is critically controlled by angiotensins, which are vasopressor peptides specifically released by the enzyme renin from the tail of angiotensinogen-a non-inhibitory member of the serpin family of protease inhibitors. Although angiotensinogen has long been regarded as a passive substrate, the crystal structures solved here to 2.1 A resolution show that the angiotensin cleavage site is inaccessibly buried in its amino-terminal tail. The conformational rearrangement that makes this site accessible for proteolysis is revealed in our 4.4 A structure of the complex of human angiotensinogen with renin. The co-ordinated changes involved are seen to be critically linked by a conserved but labile disulphide bridge. Here we show that the reduced unbridged form of angiotensinogen is present in the circulation in a near 40:60 ratio with the oxidized sulphydryl-bridged form, which preferentially interacts with receptor-bound renin. We propose that this redox-responsive transition of angiotensinogen to a form that will more effectively release angiotensin at a cellular level contributes to the modulation of blood pressure. Specifically, we demonstrate the oxidative switch of angiotensinogen to its more active sulphydryl-bridged form in the maternal circulation in pre-eclampsia-the hypertensive crisis of pregnancy that threatens the health and survival of both mother and child.

A redox switch in angiotensinogen modulates angiotensin release.,Zhou A, Carrell RW, Murphy MP, Wei Z, Yan Y, Stanley PL, Stein PE, Pipkin FB, Read RJ Nature. 2010 Oct 6. PMID:20927107<ref>PMID:20927107</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2wxw" style="background-color:#fffaf0;"></div>

==See Also==
*[[Serpin 3D structures|Serpin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Carrell RW]]
[[Category: Read RJ]]
[[Category: Wei Z]]
[[Category: Zhou A]]