Serpins

Model of Serpins – active form

The serpin family of serine proteinase inhibitors control the key cascades of the blood including coagulation, complement activation, fibrinolysis and, in the case of α-1-antitrypsin, protect lung tissue against proteolytic attack.

Antithrombin-III is the first line of defence against thrombosis. Its conformational derivative, latent antithrombin, is an anti-angiogenic agent with its plasma levels giving an index of antithrombin turnover and instability.

Canterbury Scientific Ltd has long experience in the preparation and purification of serpins through its Senior Scientists, supported by colleagues from the Christchurch and University of Cambridge groups who are now consultant advisors to Canterbury Scientific.

We provide a range of clinically significant serpins for analytical and research purposes in both native and recombinant forms and welcome enquiries about further products.

Native Plasma Serpins

  1. α-1-Antitrypsin (PiMM) – Normal purified human α-1-Antitrypsin supplied in a lyophilised form.
  2. Antithrombin-III – Normal purified human antithrombin supplied in a lyophilised form.
  3. Latent Antithrombin-III – Latent antithrombin [relaxed, 6-stranded, hyperstable, lyophilised] prepared and isolated as in Blood1

Recombinant Serpins

Recombinant Serpins are supplied frozen in buffer at an appropriate pH for long-term storage. They are prepared, isolated and purified to standards of crystallisation as described in the stated references.

  • rα-1-Antitrypsin Pittsburgh (Met358Arg) Human α-1-antitrypsin with its reactive centre methionine replaced by arginine to allow thrombin specific inhibition or cleavage.2
  • rPAI-1 (Human, Wild-type or Stabilised Active Form) Plasminogen activator inhibitor-1 is the principal inhibitor of tissue plasminogen activator (tPA) and urokinase (uPA). Human PAI-1, prepared as in Structure3, or in a form stabilised by mutations4.
  • rTBG Human thyroxine-binding globulin prepared and isolated as in PNAS5.
  • rCBG (Rat or Mouse) Human corticosteroid-binding globulin gives poor yields on recombinant expression as compared to rat or mouse CBG which have a close identity in structure and function.
  • rSMB (Human Somatomedin B) Somatomedin B is the domain of vitronectin that binds to PAI-1, cell surface receptors and integrins. Crystallised in Nat Struct Biol6 and prepared as in Protein Sci7.
  • rAngiotensinogen These species-variable angiotensinogens (rHuman, rMouse, rRat) are the source in the circulation of the vasopressor angiotensin peptides. Recombinantly prepared to crystallisation standards.

References

  1. [1999] 94, 3388-96 & J Biol Chem [2003] 278, 15116-22.
  2. J Biol Chem [2003] 278:15116-22
  3. [1999] 7:111-18
  4. Berkenpas et al EMBO J. 14: 2969-77
  5. [2006]13321-26
  6. [2003] 10:541-4
  7. [2007] 16:1502–8