From Wikipedia,
the free encyclopedia.
Angiostatin is a human
protein. It is a natural
angiogenesis inhibitor (i.e.
it blocks the growth of new
blood vessels), and it is
currently underlying
clinical trials for its use in
anticancer therapy[1].
Structure
Angiostatin is a 57 kDa
fragment of a larger protein,
plasmin (itself a fragment of
plasminogen) enclosing three
to five contiguous
Kringle modules. Each module
contains two small
beta sheets and three
disulfide bonds.
Generation
Angiostatin is produced by
autoproteolytic cleavage of
plasminogen, involving
extracellular disulfide bond
reduction by
phosphoglycerate kinase.
Biological activity
Angiostatin is known to bind a
lot of proteins, especially to
angiomotin and endothelial
cell surface
ATP synthase but also
integrins,
annexin II,
C-met receptor,
NG2-proteoglycans,
tissue-type plasminogen activator,
chondroitin sulfate proteoglycans,
and
CD26. Also smaller fragments
of angiostatin has been shown to
bind several other proteins. There
is still considerable uncertainty
on its mechanism of action, but it
seems to involve for example
inhibition of endothelial cell
migration,
proliferation and induction of
apoptosis.
