- Scientific and Standardization Committee (current name)
- International Committee for the Standardization of the Nomenclature of the Blood Clotting Factors (previous name)
- International Committee on Thrombosis and Haemostasis (ICTH) (previous name)
- International Society on Thrombosis and Haemostasis (ISTH) (founder)
The SSC adopted the Roman numeral system for labeling blood clotting factors, which became the standard in professional literature. The group changed its name over various incarnations, expanding its interests in the fields of blood coagulation and haemorrhagic disorders, eventually founding the ISTH.
The SSC is a permanent committee of the ISTH and is its scientific working arm. Conducted through subcommittees and working groups, SSC activities promote cooperation among leading international scientists.
Serine proteases (or serine endopeptidases) are enzymes that cleave peptide bonds in proteins, in which serineserves as the nucleophilic amino acid at the (enzyme’s) active site. They are found ubiquitously in both eukaryotes andprokaryotes. Serine proteases fall into two broad categories based on their structure: chymotrypsin-like (trypsin-like) orsubtilisin-like. In humans, they are responsible for co-ordinating various physiological functions, including digestion, immune response, blood coagulation and reproduction.
Serpins are a group of proteins with similar structures that were first identified as a set of proteins able to inhibit proteases. The acronym serpin was originally coined because many serpins inhibit chymotrypsin-like serine proteases (serine protease inhibitors).
The first members of the serpin superfamily to be extensively studied were the human plasma proteins antithrombin andantitrypsin, which play key roles in controlling blood coagulation and inflammation, respectively. Initially, research focused upon their role in human disease: antithrombin deficiency results in thrombosis and antitrypsin deficiency causes emphysema. In 1980 Hunt and Dayhoff made the surprising discovery that both these molecules share significant amino acid sequence similarity to the major protein in chicken egg white, ovalbumin, and they proposed a new protein superfamily. Over 1000 serpins have now been identified, these include 36 human proteins, as well as molecules in plants, fungi, bacteria, archaea and certain viruses. Serpins are thus the largest and most diverse family of protease inhibitors.
While most serpins control proteolytic cascades, certain serpins do not inhibit enzymes, but instead perform diverse functions such as storage (ovalbumin, in egg white), hormone carriage proteins (thyroxine-binding globulin, cortisol-binding globulin) and molecular chaperones (HSP47). The term serpin is used to describe these latter members as well, despite their noninhibitory function.
As serpins control processes such as coagulation and inflammation, these proteins are the target of medical research. However, serpins are also of particular interest to the structural biology and protein folding communities, because they undergo a unique and dramatic change in shape (or conformational change) when they inhibit target proteases. This is unusual — most classical protease inhibitors function as simple “lock and key” molecules that bind to and block access to the protease active site (see, for example, bovine pancreatic trypsin inhibitor). While the serpin mechanism of protease inhibition confers certain advantages, it also has drawbacks, and serpins are vulnerable to mutations that result in protein misfolding and the formation of inactive long-chain polymers (serpinopathies). Serpin polymerisation reduces the amount of active inhibitor, as well as accumulation of serpin polymers, causing cell death and organ failure. For example, the serpin antitrypsin is primarily produced in the liver, and antitrypsin polymerisation causes liver cirrhosis. Understanding serpinopathies also provides insights on protein misfolding in general, a process common to many human diseases, such as Alzheimer’s and Creutzfeldt-Jakob disease.
Streptokinase (SK) is an enzyme secreted by several species of streptococci that can bind and activate humanplasminogen. SK is used as an effective and inexpensive thrombolysis medication in some cases of myocardial infarction(heart attack) and pulmonary embolism. Streptokinase belongs to a group of medications known as fibrinolytics, and complexes of streptokinase with human plasminogen can hydrolytically activate other unbound plasminogen by activating through bond cleavage to produce plasmin. There are three domains to Streptokinase, denoted α (residues 1–150), β (residues 151–287), and γ (residues 288–414). Each domain binds plasminogen, although none can activate plasminogen independently.
It is on the World Health Organization’s List of Essential Medicines, a list of the most important medication needed in a basic health system.