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Dr. Peter G.W. Gettins
Professor Emeritus

  • Director, Center for Structural Biology
  • D. Phil,1979, Oxford University
  • Postdoctoral, Yale

Major Interests:
Structure and function of the serpin superfamily. Antithrombin structure, function and dysfunction. Structure, specificity and function of the LDL receptor-related protein LRP and its protein ligands. Use of NMR and other spectroscopic methods, as well as kinetic and thermodynamic approaches to determine structure/function correlations in solution. Use of x-ray crystallography as complement to solution studies.

1. Serpins. Serpins are large proteins (45-100kDa) that act as inhibitors, and thus regulators, of important physiological processes such as blood coagulation and fibrinolysis, and that employ a remarkable conformational change mechanism for inhibition of target proteinases. Serpins being currently studied are antithrombin, alpha-1-antitrypsin (alpha-1-proteinase inhibitor),crmA, pigment epithelium derived factor (PEDF) and heparin cofactor II. Antithrombin is the principal inhibitor of the blood coagulation proteinases thrombin and factor Xa; alpha-1-antitrypsin is the principal inhibitor of neutrophil elastase; crmA (cytokine response modifier A) is a viral serpin that the virus uses to arrest cell death of the host by inhibition of caspases and granzyme B proteinases that normally orchestrate cell death; pigment epithelium derived factor is a non-inhibitory member of the serpin superfamily that has potent anti-angiogenic activity and neurite outgrowth-promoting activity; heparin cofactor II is another plasma inhibitor of thrombinthat is activated by various glycosaminoglycans.

Questions being addressed are:

  • What are the structures of serpin-proteinase complexes, and how general are they for different serpin-proteinase pairs?
  • What are the structural changes in the proteinase responsible for inhibition?
  • What is the heparin activation mechanism of antithrombin?
  • What is the activation mechanism of heparin cofactor II?
  • Why are some serpins such as PEDF non-inhibitory?
  • What role does the serpin structure play in physiologically important serpins such as PEDF?

Methods being used are:

  • Fluorescence
  • NMR
  • X-ray crystallography
  • Kinetics
  • Site-directed mutagenesis
  • Calorimetry

2. LRP. LRP is a 600kDa multidomain receptor of the LDL receptor family. It binds and clears from circulation an extremely wide range of unrelated protein ligands, including serpin-proteinase complexes, the 720kDa non-specific proteinase inhibitor alpha-2-macroglobulin when complexed with proteinases, certain lipoproteins,the 39kDa chaperone protein RAP( receptor associated protein) as well as a number of other ligands. We are interested in determining the structural basis for the ability of LRP to bind to such a wide range of unrelated proteins. To address this we are detemining the structure of domains of LRP that bind ligands and of complexes of these domains, whether single or larger species, in complex with target protein ligands .

Methods being used are:

  • NMR spectroscopy
  • X-ray crystallography
  • Calorimetry
  • Fluorescence

UIC Center for Structural Biology
Major Instrumentation


Office: 312-996-5534


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