Ser/Thr Protease

Serine proteases are proteases in which one of the conserved amino acids in the active site of the enzyme is serine. Three major classes have been defined based on the physicochemical properties of the P1 site, trypsin-like (positively charged residues Lys/Arg preferred at P1), elastase-like (small hydrophobic residues Ala, Val at P1) or chymotrypsin-like (large hydrophobic residues Phe/Tyr/Leu at P1). The serine proteases are characterized by a catalytic triad of residues (Ser195, His57 and Asp102, chymotrypsin numbering system) that is responsible for amide bond hydrolysis. Threnonine proteases are a family of proteolytic enzymes harbouring a threonine (Thr) residue within the active site. The prototype members of this class of enzymes are the catalytic subunits of the proteasome, however the acyltransferases convergently evolved the same active site geometry andmechanism.

1049788-58-0
LCH7749944 HCl
1049788-58-0
1161921-82-9
BAY 85-8501
1161921-82-9
118409-62-4
AG 126
118409-62-4
1267949-42-7
DW532
1267949-42-7
1312691-41-0
1312691-41-0
1313881-70-7
ARQ-092
1313881-70-7
B0084-475321
CFI-400945
1338806-73-7
B0084-475334
GSK583
1346547-00-9
B0084-475340
SKLB-1028
1350544-93-2
138154-55-9
138154-55-9
1430741-35-7
CFI-401870
1430741-35-7
1431727-04-6
PLS-123
1431727-04-6
1434048-34-6
GDC-0853
1434048-34-6
1446790-62-0
RO9021
1446790-62-0
1554458-53-5
BAY-1217389
1554458-53-5

Background


An Overview of Ser/Thr Protease

Serine/threonine protease (Ser/Thr Protease) is a class of enzymes that phosphorylate serine or threonine hydroxyl groups in a particular substrate protein. Specifically, serine (Ser) proteases are a class of proteolytic enzymes with serine as the active center. They play an important role in the life activities of mammals, such as in digestion, coagulation, apoptosis and the replenishment system. The role of Serine proteases is to break peptide bonds in macromolecular proteins, making them small molecule proteins. Trypsin, chymotrypsin, elastase, and thrombin in animals are all serine proteases. Their active sites contain Ser, His, Asp, and have the same catalytic mechanism, but the substrate binding sites are different. Threnonine (Thr) protease is a proteolytic enzyme that contains a threonine residue in the active center. The prototype member of this type of enzyme is the catalytic subunit of the proteasome, whereas the acyltransferase will evolve the same active center geometry and mechanism.

Inhibition of Ser/Thr Protease

Ser protease inhibitors are widely found in animals, plants and microorganisms and are capable of regulating serine protease activity. Ser protease inhibitors play a role in a variety of physiological processes including food digestion, blood coagulation, pathogen transmission, inflammatory response and immune response. There are many Ser/Thr Protease inhibitors suitable for many related diseases. For example, Nafamostat is a broad-spectrum serine protease inhibitor and a kallikrein inhibitor that inhibits blood clotting. Upamostat is another serine protease inhibitor, Which is an orally active prodrug and a urokinase-type plasminogen activator (uPA) inhibitor. Therefore, Serine/threonine protease will be a key target for diseases.

Ser/Thr Protease and diseases

Ser proteases play important roles in regulating many important life processes in organisms, such as protein folding, hemagglutination, complement activation, inflammatory response, cell migration, cell matrix remodeling, and tumor suppression.

Reference:

Whisstock, J. C., Silverman, G. A., Bird, P. I., Bottomley, S. P., Kaiserman, D., Luke, C. J., Pak, S. C., Reichhart, J. M., Huntington, J. A. (2010). Serpins flex their muscle: II. Structural insights into target peptidase recognition, polymerization, and transport functions. The Journal of Biological Chemistry. 285 (32): 24307–14312.