2WY1
Crystal structure of rat angiotensinogen in P321 space group
Summary for 2WY1
| Entry DOI | 10.2210/pdb2wy1/pdb |
| Related | 2WXW 2WXX 2WXY 2WXZ 2WY0 2X0B |
| Descriptor | ANGIOTENSINOGEN (1 entity in total) |
| Functional Keywords | hormone, renin, angiotensin, hypertension, glycoprotein, vasoconstrictor, vasoactive |
| Biological source | RATTUS NORVEGICUS (RAT) |
| Cellular location | Secreted: P01015 |
| Total number of polymer chains | 2 |
| Total formula weight | 99176.55 |
| Authors | Zhou, A.,Wei, Z.,Carrell, R.W.,Read, R.J. (deposition date: 2009-11-11, release date: 2010-10-20, Last modification date: 2024-10-16) |
| Primary citation | Zhou, A.,Carrell, R.W.,Murphy, M.P.,Wei, Z.,Yan, Y.,Stanley, P.L.,Stein, P.E.,Pipkin, F.B.,Read, R.J. A Redox Switch in Angiotensinogen Modulates Angiotensin Release. Nature, 468:108-, 2010 Cited by PubMed 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 Å 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 Å 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. PubMed: 20927107DOI: 10.1038/NATURE09505 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.15 Å) |
Structure validation
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