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

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)
Angiotensinogen(Gene symbol: Agt)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB