SSI protease inhibitor
{{Infobox protein family
| Symbol = SSI
| Name = SSI
| image = PDB 5sic EBI.jpg
| width =
| caption = Molecular recognition at the active site of subtilisin BPN': crystallographic studies using genetically engineered protease inhibitor SSI (Streptomyces subtilisin inhibitor)
| Pfam = PF00720
| Pfam_clan =
| InterPro = IPR000691
| SMART =
| PROSITE = PDOC00766
| MEROPS = I16
| SCOP = 2sic
| TCDB =
| OPM family =
| OPM protein =
| CAZy =
| CDD =
}}
In molecular biology the protein SSI is a Subtilisin inhibitor-like which stands for Streptomyces subtilisin inhibitor. This is a protease inhibitor. These are often synthesised as part of a larger precursor protein, either as a prepropeptide. The function of this protein domain is to prevent access of the substrate to the active site. It is found only in bacteria.
Function
SSI is a protease inhibitor, it prevents enzymes from acting on a substrate. Some SSI's also inhibit trypsin, chymotrypsin and griselysin.{{cite journal |author1=Rawlings ND |author2=Tolle DP |author3=Barrett AJ | title = Evolutionary families of peptidase inhibitors | journal = Biochem. J. | volume = 378 | issue = Pt 3 | pages = 705–16 |date=March 2004 | pmid = 14705960 | pmc = 1224039 | doi = 10.1042/BJ20031825 }}{{cite journal |author1=Kojima S |author2=Nishiyama Y |author3=Kumagai I |author4=Miura K | title = Inhibition of subtilisin BPN' by reaction site P1 mutants of Streptomyces subtilisin inhibitor | journal = J. Biochem. | volume = 109 | issue = 3 | pages = 377–82 |date=March 1991 | pmid = 1908859 | doi = 10.1093/oxfordjournals.jbchem.a123389}} Commercially, SSI's have huge potential in the commercial market, they help stabilise proteases in products such as laundry detergents to prevent autolysis of biological washing powders.{{cite journal |vauthors=Ganz PJ, Bauer MD, Sun Y, Fieno AM, Grant RA, Correa PE, etal | title=Stabilized variant of Streptomyces subtilisin inhibitor and its use in stabilizing subtilisin BPN'. | journal=Protein Eng Des Sel | year= 2004 | volume= 17 | issue= 4 | pages= 333–9 | pmid=15187224 | doi=10.1093/protein/gzh045 | doi-access=free }} This means that the enzymes in the washing powder are kept in optimum performance.
Structure
SSI is a homodimer, in other words, it is made of two subunits which are exactly the same as each other. Each monomer contains 2 antiparallel beta-sheets and 2 short alpha-helices. Protease binding induces the widening of a channel-like structure, in which hydrophobic side-chains are sandwiched between 2 lobes.{{cite journal |author1=Hirono S |author2=Akagawa H |author3=Mitsui Y |author4=Iitaka Y | title = Crystal structure at 2.6 A resolution of the complex of subtilisin BPN' with streptomyces subtilisin inhibitor | journal = J. Mol. Biol. | volume = 178 | issue = 2 | pages = 389–414 |date=September 1984 | pmid = 6387152 | doi = 10.1016/0022-2836(84)90150-5}}
Studies have shown that the loss of the C-terminal domain reduces the inhibitory effect of the proteins. This implies that the C-terminal domain is responsible for maintaining the correct 3D fold.{{cite journal |author1=Sakai M |author2=Odani S |author3=Ikenaka T | title = Importance of the carboxyl-terminal four amino acid residues in the inhibitory activity of Streptomyces subtilisin inhibitor (with a revision of its carboxyl-terminal sequence) | journal = J. Biochem. | volume = 87 | issue = 3 | pages = 891–8 |date=March 1980 | pmid = 6993452 | doi = 10.1093/oxfordjournals.jbchem.a132819}}
Structural similarities between the primary and secondary contact loops of SSI, and the ovomucoid and pancreatic secretory trypsin inhibitor family suggest evolution of the 2 families from a common ancestor.