Angiostatin is a naturally occurring protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 found in several animal species, including humans. It is an endogenous angiogenesis inhibitor

Angiogenesis inhibitor

An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels . Some angiogenesis inhibitors are a normal part of the body's control, some are administered as drugs, and some come from diet....

 (i.e., it blocks the growth of new blood vessel

Blood vessel

The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...

s), and it is currently undergoing clinical trial

Clinical trial

Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...

s for its use in anticancer therapy.

Structure

Angiostatin is a 38 kDa fragment of a larger protein, plasmin

Plasmin

Plasmin is an important enzyme present in blood that degrades many blood plasma proteins, most notably, fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein is encoded by the PLG gene.- Function :...

 (itself a fragment of plasminogen) enclosing three to five contiguous Kringle

Kringle

Kringle is a Scandinavian pastry, a Nordic variety of pretzel, which arrived with Roman Catholic monks in the 13th century, especially in Denmark...

 modules. Each module contains two small beta sheet

Beta sheet

The β sheet is the second form of regular secondary structure in proteins, only somewhat less common than the alpha helix. Beta sheets consist of beta strands connected laterally by at least two or three backbone hydrogen bonds, forming a generally twisted, pleated sheet...

s and three disulfide bond

Disulfide bond

In chemistry, a disulfide bond is a covalent bond, usually derived by the coupling of two thiol groups. The linkage is also called an SS-bond or disulfide bridge. The overall connectivity is therefore R-S-S-R. The terminology is widely used in biochemistry...

s.

Generation

Angiostatin is produced, for example, by autoproteolytic cleavage of plasminogen, involving extracellular disulfide bond reduction

Redox

Redox reactions describe all chemical reactions in which atoms have their oxidation state changed....

 by phosphoglycerate kinase

Phosphoglycerate kinase

Phosphoglycerate kinase is a transferase enzyme used in the seventh step of glycolysis. It transfers a phosphate group from 1,3-bisphosphoglycerate to ADP, forming ATP and 3-Phosphoglycerate....

. Furthermore, angiostatin can be cleaved from plasminogen by different metalloproteinase

Metalloproteinase

Metalloproteinases constitute a family of enzymes from the group of proteases, classified by the nature of the most prominent functional group in their active site. These are proteolytic enzymes whose catalytic mechanism involves a metal. Most metalloproteases are zinc-dependent, but some use...

s (MMPs), elastase

Elastase

In molecular biology, elastase is an enzyme from the class of proteases that break down proteins.- Forms and classification:There exist eight human genes for elastase:Bacterial forms: Organisms such as P...

, prostate-specific antigen (PSA), 13 KD serine protease

Serine protease

Serine proteases are enzymes that cleave peptide bonds in proteins, in which serine serves as the nucleophilic amino acid at the active site.They are found ubiquitously in both eukaryotes and prokaryotes...

, or 24KD endopeptidase

Endopeptidase

Endopeptidase or endoproteinase are proteolytic peptidases that break peptide bonds of nonterminal amino acids , in contrast to exopeptidases, which break peptide bonds from their end-pieces. For this reason, endopeptidases cannot break down peptides into monomers, while exopeptidases can break...

.

Biological activity

Angiostatin is known to bind many proteins, especially to angiomotin

Angiomotin

Angiomotin is a 675-residue protein that increases the random migration of endothelial cells as well as the migration of endothelial cells toward growth factors....

 and endothelial cell surface ATP synthase

ATP synthase

right|thumb|300px|Molecular model of ATP synthase by X-ray diffraction methodATP synthase is an important enzyme that provides energy for the cell to use through the synthesis of adenosine triphosphate . ATP is the most commonly used "energy currency" of cells from most organisms...

 but also integrin

Integrin

Integrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the ECM. They also play a role in cell signaling and thereby regulate cellular shape, motility, and the cell cycle....

s, annexin

Annexin

Annexin is a common name for a group of cellular proteins. They are found in all kingdoms with the exception of the bacteria....

 II, C-met receptor, NG2-proteoglycans, tissue-type plasminogen activator, chondroitin sulfate proteoglycans, and CD26. Additionally, smaller fragments of angiostatin may bind several other proteins. There is still considerable uncertainty on its mechanism of action, but it seems to involve inhibition of endothelial cell migration, proliferation

Cell growth

The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...

 and induction of apoptosis

Apoptosis

Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

. It has been proposed that angiostatin activity is related, among other things, to the coupling of its mechanical and redox properties.