• Introduction to Protein Structure and Function
• 40 min
  1. Nature’s strategies in the regulation of enzyme activity by modifiers

  • Prof. Antonio Baici
• Creation of Protein Variability by Manipulation of Genes
• 28 min
  2. Understanding protein variability through functional analysis of random mutagenesis

  • Prof. Andrew Kaplan
• 48 min
  3. Perspectives on biological catalysis

  • Prof. Stephen Benkovic
• 45 min
  4. Fundamentals and principles for engineering proteolytic activity

  • Prof. Charles Craik
• Metabolic Diseases Caused by Genetic Mutation
• 36 min
  5. Modifications of pyruvate handling in health and disease

  • Prof. Mary Sugden
• 29 min
  6. Mitochondrial fatty acid oxidation deficiencies

  • Prof. Niels Gregersen
• 33 min
  7. Inborn errors of ketone body metabolism

  • Prof. Toshiyuki Fukao
• 34 min
  8. Cathepsin K in bone and joint diseases

  • Prof. Dieter Bromme
• 22 min
  9. Fabry disease: alfa-galactosidase A deficiency and enzyme replacement therapy

  • Prof. David Warnock
• 47 min
  10. Acid beta-glucosidase/glucocerebrosidase (GCase)

  • Prof. Gregory Grabowski
• 23 min
  11. GM2 gangliosidosis future treatments 1

  • Prof. Brian Mark
• 19 min
  12. GM2 gangliosidosis future treatments 2

  • Prof. Brian Mark
• 29 min
  13. The neuronal ceroid lipofuscinoses

  • Prof. Sandra Hofmann
• Disorders of Blood Coagulation
• 24 min
  14. Advances in fibrinolysis

  • Dr. Paul Kim
• 26 min
  15. Tissue factor and factor VII: initiation of blood coagulation

  • Dr. John McVey
• 36 min
  16. Structure of thrombin, a Janus-headed proteinase

  • Prof. Wolfram Bode
• 45 min
  17. The protein c-thrombomodulin mechanism: regulating multiple biological systems

  • Prof. Edward Conway
• 40 min
  18. Fibrinogen and factor XIII

  • Prof. John Weisel
• 31 min
  19. Factor VIII and haemophilia A

  • Dr. Geoffrey Kemball-Cook
• 34 min
  20. Factor IX

  • Prof. Bruce Furie
• 42 min
  21. The biology and pathobiology of von Willebrand factor

  • Prof. David Lillicrap
• 40 min
  22. Thrombotic thrombocytopenic purpura

  • Prof. J. Evan Sadler
• 26 min
  23. Fibrinolysis

  • Prof. Edward Tuddenham
• Other Molecular and Metabolic Disorders
• 45 min
  24. Glucose-6-phosphate dehydrogenase deficiency

  • Dr. Jane Leopold
• 26 min
  25. Cytochrome b5 reductase deficiency and hereditary methemoglobinemia

  • Dr. Scott Reading
• 50 min
  26. Sickle cell disease

  • Prof. Martin H. Steinberg
• 40 min
  27. Pyruvate kinase deficiency

  • Prof. Alberto Zanella
• 47 min
  28. Heritable disorders of collagen

  • Dr. Heather Yeowell
• 40 min
  29. Duchenne muscular dystrophy

  • Prof. Jeff Chamberlain
• Archived Lectures *These may not cover the latest advances in the field
• 33 min
  30. Protein crystallography

  • Prof. Michael James
• 48 min
  31. Regulation of blood coagulation by the serpin, antithrombin

  • Prof. Steve Olson
• 37 min
  32. Rhodopsin and retinitis pigmentosa

  • Dr. Shalesh Kaushal
• 40 min
  33. The physiology and pathology of coagulation factor XI

  • Dr. David Gailani
• 24 min
  34. Cytochrome b5 reductase deficiency and hereditary methemoglobinemia

  • Prof. Josef Prchal
• 49 min
  35. Metachromatic leukodystrophy

  • Prof. Volkmar Gieselmann
• 21 min
  36. Serpins and serpinopathies

  • Dr. James Whisstock
• 27 min
  37. Multiple acyl-CoA dehydrogenation deficiency: defects of electron transfer flavoproteins

  • Dr. Rikke Olsen
• 39 min
  38. Pleiotropic and epistatic genes in sickle cell anaemia

  • Prof. Ronald Nagel
• 44 min
  39. Genetic disorders of carbonic anhydrases II and IV

  • Prof. William Sly
• 39 min
  40. GM2 gangliosidoses

  • Prof. Don Mahuran
• 48 min
  41. Kinetic analysis of protein activity

  • Prof. Antonio Baici

Printable Handouts

PDF

Navigable Slide Index

1. Introduction
2. Blood hemostasis
3. Activation of procoagulant factors by injury
4. Anticoagulant factors
5. The role of antithrombin and heparan sulfate
6. Antithrombin
7. Inherited deficiencies of antithrombin
8. Mutations causing antithrombin dysfunction
9. Serpins: proteolytic enzymes regulators
10. Serpins characteristics
11. Lock-and-key vs.serpin type protease inhibitors
12. Serpin type protease inhibitors structure
13. Inhibition mechanism through antithrombin activity
14. Heparin/heparan sulfate structure
15. Activation of antithrombin
16. X-ray structure of the antithrombin-heparin complex
17. Close-up of the heparin binding site of antithrombin
18. Antithrombin "hotspots" binding heparin
19. Heparin binds antithrombin in a two-step process
20. Antithrombin hotspots contribute to heparin binding
21. Effect of saccharides: antithrombin-heparin affinity
22. The induced-conformational change binding
23. Pre-equilibrium binding mechanism
24. Allosteric activation of antithrombin by heparin
25. Effect of heparin on antithrombin reactivity
26. Activation mechanisms of antithrombin by heparin
27. The bridging mechanism
28. The conformational activation mechanism (1)
29. The conformational activation mechanism (2)
30. Hypothesis: reactivity enhancment by reactive loop
31. Results of the hypothesis tested
32. Modified conformational activation mechanism
33. Mapping the antithrombin exosite (1)
34. Mapping the antithrombin exosite (2)
35. Localization of the exosite of antithrombin
36. Two residues mutants affect antithrombin reactivity
37. Antithrombin/heparin/FXa complexes structures
38. Heparin activation of antithrombin: summary
39. Conserved residues in the reactive loop sequences
40. Limited reactivity of serpin by the AT reactive loop
41. Molecular basis for antithrombin selective reactivity
42. Negative features of heparin anticoagulant thepray
43. Reference (1)
44. Reference (2)
45. Reference (3)

Topics Covered

• Antithrombin and hemostasis
• Dysfunctional antithrombins and thrombophilia
• Protease regulation by serpins
• Heparin requirement for antithrombin function
• Structural determinants of heparin binding to antithrombin
• Heparin-induced conformational changes in antithrombin
• Heparin as an allosteric activator of antithrombin
• Bridging and conformational change mechanisms of heparin activation of antithrombin
• Structural basis of conformational activation
• Role of exosites in conformational activation
• Role of the reactive loop in antithrombin anticoagulant function
• Implications for improved heparin anticoagulants

Links

Series:

• Protein Epidemiology

Categories:

• Biochemistry
• Cell Biology
• Clinical Practice

Therapeutic Areas:

• Haematology

Talk Citation

Publication History

• Published on October 1, 2007
• Archived on April 27, 2016

Financial Disclosures

• Prof. Steve Olson has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.