Protease inhibitor (biology)

Peptidase inhibitor I9
subtilisin bpn' prosegment (77 residues) complexed with a mutant subtilisin bpn' (266 residues). crystal ph 4.6. crystallization temperature 20 c diffraction temperature-160 c
Identifiers
Symbol	Inhibitor_I9
Pfam	PF05922
InterPro	IPR010259
MEROPS	I9
SCOP	1gns
SUPERFAMILY	1gns
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Serine endopeptidase inhibitors
solution structure of marinostatin, a protease inhibitor, containing two ester linkages
Identifiers
Symbol	Inhibitor_I10
Pfam	PF12559
InterPro	IPR022217
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Cathepsin propeptide inhibitor domain (I29)
crystal structure of a cysteine protease proform
Identifiers
Symbol	Inhibitor_I29
Pfam	PF08246
InterPro	IPR013201
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Saccharopepsin inhibitor I34
the structure of proteinase a complexed with a ia3 mutant inhibitor
Identifiers
Symbol	Inhibitor_I34
Pfam	PF10466
InterPro	IPR019507
MEROPS	I34
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

In biology and biochemistry, protease inhibitors are molecules that inhibit the function of proteases. Many naturally occurring protease inhibitors are proteins.

In medicine, protease inhibitor is often used interchangeably with alpha 1-antitrypsin (A1AT, which is abbreviated PI for this reason). A1AT is indeed the protease inhibitor most often involved in disease, namely in alpha 1-antitrypsin deficiency.

Protease inhibitors may be classified either by the type of protease they inhibit, or by their mechanism of action. In 2004 Rawlings and colleagues introduced a classification of protease inhibitors based on similarities detectable at the level of amino acid sequence. This classification initially identified 48 families of inhibitors that could be grouped into 26 related superfamily (or clans) by their structure. According to the MEROPS database there are now 85 families of inhibitors. These families are named with an I followed by a number, for example, I14 contains hirudin-like inhibitors.

Classes of proteases are:

Classes of inhibitor mechanisms of action are:

This is a family of protease suicide inhibitors called the serpins. It contains inhibitors of multiple cysteine and serine protease families. Their mechanism of action relies on undergoing a large conformational change which inactivates their target's catalytic triad.

Proteinase propeptide inhibitors (sometimes referred to as activation peptides) are responsible for the modulation of folding and activity of the peptidase pro-enzyme or zymogen. The pro-segment docks into the enzyme, shielding the substrate binding site, thereby promoting inhibition of the enzyme. Several such propeptides share a similar topology, despite often low sequence identities. The propeptide region has an open-sandwich antiparallel-alpha/antiparallel-beta fold, with two alpha-helices and four beta-strands with a (beta/alpha/beta)x2 topology. The peptidase inhibitor I9 family contains the propeptide domain at the N-terminus of peptidases belonging to MEROPS family S8A, subtilisins. The propeptide is removed by proteolytic cleavage; removal activating the enzyme.