2WY1: Crystal Structure Of Rat Angiotensinogen In P321 Space Group

Citation:
Abstract
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.
PDB ID: 2WY1Download
MMDB ID: 85560
PDB Deposition Date: 2009/11/11
Updated in MMDB: 2010/11
Experimental Method:
x-ray diffraction
Resolution: 3.15  Å
Source Organism:
Similar Structures:
Biological Unit for 2WY1: monomeric; determined by software (PISA)
Molecular Components in 2WY1
Label Count Molecule
Protein (1 molecule)
1
Angiotensinogen(Gene symbol: Agt)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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