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Key and lock ; theory of induced fit

Key and lock ; theory of induced fit. +. Endopeptidase. Exopeptidase. Carboxypeptidase. Aminopeptidase. Proteolytic activation of zymogens. Intestine. Pancreas. Enteropeptidase. Trypsinogen. Chymotrypsinogen. Trypsin. p - Chymotrypsin. a - Chymotrypsin. Trypsin inhibitor.

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Key and lock ; theory of induced fit

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  1. Key and lock; theory of induced fit +

  2. Endopeptidase

  3. Exopeptidase Carboxypeptidase Aminopeptidase

  4. Proteolytic activation of zymogens Intestine Pancreas Enteropeptidase Trypsinogen Chymotrypsinogen Trypsin p - Chymotrypsin a - Chymotrypsin Trypsin inhibitor Inactive trypsine

  5. Chymotrypsinogen 1……………………………………………………………………..245 Trypsin p-Chymotrypsin 1…………..15 16…………………………………………..245 Chymotrypsin a-Chymotrypsin 1……….13 16…………………….146 149………245

  6. Chymotrypsin: hydrolysis of peptide and ester bonds Hydrolysis of peptide bonds Hydrolysis of ester bonds

  7. Substrate specificity of Chymotrypsin • Phe • Typ • Trp • Met

  8. Ser195 –OH of chymotrypsin reacts with DIPF CH2OH CH2 Ser 195 Ser 195

  9. Kinetics of chymotrypsin catalysis (measured with synthetic substrate)

  10. Kinetics of chymotrypsin catalysis (measured with synthetic substrate) A Steady state Burst phase Time [milisecundum]

  11. Two stages of the enzyme action Enzyme Acyl-enzyme Enzyme

  12. Chymotrypsin active site & its function

  13. Hydrolysis of peptide bond – by chymotrypsin

  14. Hydrolysis of peptide bond – by chymotrypsin Acyl – enzyme intermedier Acyl – enzyme intermedier Tetrahedral - intermedier

  15. Hydrolysis of peptide bond – by chymotrypsin

  16. Homolog enzymes • Chymotrypsin – Phe, Tyr, Trp, Met • Trypsin - Arg, Lys • Elastase –amino acids with short side chain residues ie.: Ala, Ser • Thrombin –Fibrinogen, V, VIII, PC • Plasmin -Fibrin,

  17. Substrate bingind site S1 of chymotrypsin, trypsin & elastase O O Val 216 Asp 189 Val 190 Chymotrypsin Trypsin Elastase

  18. Cystein, aspartyl & metalloproteases • Papain isolated from papaya • Nucleophyl attack on peptide bond • Cathepsins – immunsystem • Caspases - apoptoses

  19. Cistein, aspartyl & metalloproteases • Asp – protonated • Asp – deprotonated • H2O • Renin • Pepsin

  20. Cistein, aspartyl & metalloproteases • Bacterial termolysine • Carboxypeptidase A • Zinc proteases (matrix metalloproteinases MMP) • MMP – tissue degradation and remodelling

  21. Cholinerg synapsis Presynaptical membrane Postsynaptical membrane

  22. Acetylcholine esterase • Synaptic cleft • Bound to collagen GAG network • Hydrolysis of Acethylcholine • a2b2 • Turnovernumber: 25000 / sec Acetilkolin receptor

  23. Catalytic mechanism of acetylcholine esterase

  24. Organic phosphate inhibitors of acetylcholine esterase • Sarin – Metro of Tokyo • Tabun • extremely toxic substance • it is classified as a weapon of mass destruction • Parathion – pesticide • Labelled DIFP • 12000 / mm2 receptor/mouse diafragma

  25. Carbamoylation of Ser-OH in acetylcholine esterase Physostigmin (Eserin) Slow hydrolysis of carbamoyl-enzyme intermedier Ordeal In witchcraft trials

  26. Carbamoylation of Ser-OH in acetylcholine esterase by neostigmin Neostigmin Slow hydrolysis of carbamoyl-enzyme intermedier: it inhibits acetylcholine esterase, [acetylcholine] increase; Decrease in intraocular pressure

  27. Dekametonium: bounds to receptor Constant depolarisation Succinylcholine: slow hydrolysis Pseudocholine esterase

  28. Zymogens of pancreas

  29. Enteropeptidase Trypsin Trypsinogen Proelastase Elastase Procarboxypeptidase Carboxypeptidase Prolipase Lipase Cymotrypsin Cymotrypsinogen

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