Serine Protease Inhibitors

Serine Protease Inhibitors

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 and antitrypsin, which play key roles in controlling blood coagulation (e.g. Figure 1) 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 tumor suppressor genes (maspin). 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.

Read more about Serine Protease InhibitorsCross-class Inhibitors, Localization and Roles, Structure, Conformational Change and Inhibitory Mechanism, Conformational Modulation of Serpin Activity, Serpin Receptor Interactions, Conformational Change and Non-inhibitory Function, Serpins, Serpinopathies and Human Disease, Development of Therapeutic Strategies To Combat Serpinopathies, Mutations That Result in Spontaneous Formation of Latent (or Latent-like), Inactive Conformations, Other Mechanisms of Serpin-related Disease, Evolution

Other articles related to "serine protease inhibitor, protease, inhibitors, serine, serine protease, protease inhibitor, serine protease inhibitors, inhibitor, proteases":

LEKTI - Structure and Function
... LEKTI is a large multidomain serine protease inhibitor expressed in stratified epithelial tissue ... that are cleaved into smaller, functional fragments by the protease furin ... responsible for 3 intramolecular disulphide bonds characteristic of Kazal-type related inhibitors ...
Protease Research
... The field of protease research is enormous ... For a look at current activities and interests of protease researchers, see the International Proteolysis Society web page ...
TMPRSS2
... Transmembrane protease, serine 2 is an enzyme that in humans is encoded by the TMPRSS2 gene ... This gene encodes a protein that belongs to the serine protease family ... domain, a receptor class A domain, a scavenger receptor cysteine-rich domain and a protease domain ...
Pol (HIV) - Protease
... A protease is any enzyme that cuts proteins into segments ... in their final form, but as larger combination proteins the specific protease used by HIV cleaves these into separate functional units ... Protease inhibitor drugs block this step ...
Serine Protease Inhibitors - Types of Serpins - Viral
... Studies on Crma and Serp2, reveal both are cross-class inhibitor and targets both serine (Granzyme B albeit weakly) and cysteine proteases (Caspase 1 and ...