Editing Angiostatin (section)

==Structure==
Angiostatin is a 38 kDa fragment of a larger protein, [[plasmin]] (itself a fragment of [[plasminogen]]) enclosing three to five contiguous [[kringle domain|kringle]] modules. Each module contains two small [[beta sheet]]s and three [[disulfide bond]]s.<ref>{{cite journal
| vauthors = Cao Y, Ji RW, Davidson D
| title = Kringle domains of human angiostatin. Characterization of the anti-proliferative activity on endothelial cells
| journal = The Journal of Biological Chemistry
| volume = 271
| issue = 46
| pages = 29461–7
|date=November 1996
| pmid = 8910613
| doi = 10.1074/jbc.271.46.29461
|display-authors=etal| doi-access = free
}}</ref><ref>{{cite journal
| vauthors = O'Reilly MS, Holmgren L, Shing Y
| title = Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma
| journal = Cell
| volume = 79
| issue = 2
| pages = 315–28
|date=October 1994
| pmid = 7525077
| doi = 10.1016/0092-8674(94)90200-3
| s2cid = 27799550
|display-authors=etal}}</ref>

There are four different structural variants to angiostatin differing in the combination of kringle domains: K1-3, K1-4, K1-5, K1-4 with a fragment of K-5. Each kringle domain contributes a different element of inhibition to the cytokine. Recent studies through recombinant angiostatin have shown however that K1-3 is pivotal is the inhibitory nature of angiostatin.<ref>{{Cite journal|title=The X-ray Crystallographic Structure of the Angiogenesis Inhibitor Angiostatin|issue=4|pages=1009–1017|journal=Journal of Molecular Biology|volume=318|doi=10.1016/S0022-2836(02)00211-5|date=2002-05-10 | last1 = Abad | first1 = Marta C. | last2 = Arni | first2 = R.K. | last3 = Grella | first3 = Davida K. | last4 = Castellino | first4 = Francis J. | last5 = Tulinsky | first5 = Alexander | last6 = Geiger | first6 = James H.|pmid=12054798}}</ref>

K1-3 form the “triangular bowl-like structure” of angiostatin.<ref name=":0">{{Cite journal|last1=Geiger|first1=J. H.|last2=Cnudde|first2=S. E.|date=2004|title=What the structure of angiostatin may tell us about its mechanism of action|journal=Journal of Thrombosis and Haemostasis|language=en|volume=2|issue=1|pages=23–34|doi=10.1111/j.1538-7836.2004.00544.x|pmid=14717962|s2cid=34303147|issn=1538-7836|doi-access=free}}</ref> This structure is stabilized by interactions between inter-kringle peptides and kringles, although the kringle domains do not directly interact with each other. Angiostatin is effectively divided into two sides. The active site of K1 is found on one side, while the active sites of K2 and K3 are found on the other. This is hypothesized to result in the two different functions of angiostatin. The K1 side is believed to be primarily responsible for the inhibition of cellular proliferation, while the K2-K3 sides is believed to be primarily responsible for the inhibition of cell migration.<ref name=":0" />