BEH.462/3. 962J Molecular Principles of Biomaterials Spring 2003 Breakdown by mechanism Il (SLIDE) Active Site Enzyme concentration (mg/ml) Fig. 2. Butanol production with variation in cyme concentration Hg. IL. Enzyme catalysis of cst ng the eser hydrolysis of pely (buyl cyaneacybte) (pH7,37C. What does esterase do in vivo? Enzymatic activity in vivo on peptide sequences lavage Enzyme Functions in vivo Target amino acid sequences plasminogen activator Degradation of fibrin matrices. Jon fibrinogen: Arg1o4-Asp1o5, Arg10-Val111 urokinase or tissue-type angiogenesis, tumor progression Lys206-Met207, Arg42-Ala43, Lys130- plasminogen activator)/ urokinase can bind to cell surface Glu131, Lysg4-Sera5, Lysa7-Met plasminogen→> plasmin receptor atrix metalloproteinases Facilitate cell migration ype I collagen: Gly775-lle77e soluble and cell-surface): e.g In smaller peptides: Gly-Leu or Gly lle ibroblast Collagenase(MMP I) Elastase Elastin remodeling Poly(Ala)sequences REFS for MMP: (REF J Biol Chem. 256, 9511(1981);J Biol Chem. 264, 393 (1989); J Biol. I Chem. 266, 6747(1991)) Note that proteases often have complementary protease inhibitors e.g. plasminogen activators inhibited by plasminogen activator inhibitor type-1(a serine protease inhibitor) Lecture 4- Biological Recognition pt. 2 4 of 9BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 • Breakdown by mechanism II Mechanism: data on degradation of 250nm-diam. porous particles: (SLIDE) • What does esterase do in vivo? Enzymatic activity in vivo on peptide sequences: 5,6 Cleavage Enzyme Functions in vivo Target amino acid sequences Plasminogen activator (urokinase or tissue-type plasminogen activator) / plasminogen → plasmin Degradation of fibrin matrices, angiogenesis, tumor progression; urokinase can bind to cell surface receptor on fibrinogen: Arg104-Asp105, Arg110-Val111, Lys206-Met207, Arg42-Ala43, Lys130- Glu131, Lys84-Ser85, Lys87-Met88 Matrix metalloproteinases (soluble and cell-surface): e.g. Fibroblast Collagenase (MMP I) Facilitate cell migration Type I collagen: Gly775-Ile776 In smaller peptides: Gly-Leu or Gly Ile bonds Elastase Elastin remodeling Poly(Ala) sequences REFS for MMP: (REF J. Biol. Chem. 256, 9511 (1981); J. Biol. Chem. 264, 393 (1989); J. Biol.l Chem. 266, 6747 (1991)) Note that proteases often have complementary protease inhibitors: e.g. plasminogen activators inhibited by plasminogen activator inhibitor type-1 (a serine protease inhibitor) Lecture 4 – Biological Recognition pt. 2 4 of 9