Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.6.1.44 (
AGT
)
770
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
In the present study, we have investigated the in vitro polymerization of human plasma
AGT
(angiotensinogen), a non-inhibitory member of the serpin (SERine Protease INhibitor) family. Polymerization of
AGT
is thought to contribute to a high molecular mass form of the protein in plasma that is increased in pregnancy and pregnancy-associated hypertension. The results of the present study demonstrate that the polymerization of
AGT
occurs through a novel mechanism which is primarily dependent on non-covalent linkages, while additional disulfide linkages formed after prolonged incubation are not essential for either formation or stability of polymers. We present the first analyses of
AGT
polymers by electron microscopy, CD spectroscopy, stability assays and sensitivity to proteinases and we conclude that their structure differs from the 'loop-sheet' polymers typical of inhibitory serpins.
Histidine
residues within the unique N-terminal extension of
AGT
appear to influence polymer formation, although polymer formation can still take place after their removal by renin. At a functional level, we show that
AGT
polymers are not substrates for renin, so polymerization of
AGT
in plasma would predictably lead to decreased formation of AngI (angiotensin I) with blood pressure lowering. Polymerization may therefore be an appropriate response to hypertension. The ability of
AGT
to protect its renin cleavage site through polymerization may explain why the AngI decapeptide has remained linked to the large and apparently inactive serpin body throughout evolution.
...
PMID:Polymerization of human angiotensinogen: insights into its structural mechanism and functional significance. 1687 75
