2x0b: Difference between revisions
New page: '''Unreleased structure''' The entry 2x0b is ON HOLD Authors: Zhou, A., Wei, Z., Yan, Y., Carrell, R.W., Read, R.J. Description: Crystal structure of human angiotensinogen complexed wi... |
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The | ==Crystal structure of human angiotensinogen complexed with renin== | ||
<StructureSection load='2x0b' size='340' side='right'caption='[[2x0b]], [[Resolution|resolution]] 4.33Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2x0b]] is a 8 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=2X0B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2X0B 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]] 4.33Å</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=2x0b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x0b OCA], [https://pdbe.org/2x0b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2x0b RCSB], [https://www.ebi.ac.uk/pdbsum/2x0b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2x0b ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/RENI_HUMAN RENI_HUMAN] Defects in REN 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> Defects in REN are the cause of familial juvenile hyperuricemic nephropathy type 2 (HNFJ2) [MIM:[https://omim.org/entry/613092 613092]. It is a renal disease characterized by juvenile onset of hyperuricemia, slowly progressive renal failure and anemia.<ref>PMID:19664745</ref> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/RENI_HUMAN RENI_HUMAN] Renin is a highly specific endopeptidase, whose only known function is to generate angiotensin I from angiotensinogen in the plasma, initiating a cascade of reactions that produce an elevation of blood pressure and increased sodium retention by the kidney. | |||
<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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2x0b" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Renin|Renin]] | |||
*[[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: Yan Y]] | |||
[[Category: Zhou A]] | |||