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Fundamentals of Biochemistry Third Edition Fundamentals of Biochemistry Third Edition Chapter 11 Enzymatic Catalysis Chapter 11 Enzymatic Catalysis Copyright.

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Presentation on theme: "Fundamentals of Biochemistry Third Edition Fundamentals of Biochemistry Third Edition Chapter 11 Enzymatic Catalysis Chapter 11 Enzymatic Catalysis Copyright."— Presentation transcript:

1 Fundamentals of Biochemistry Third Edition Fundamentals of Biochemistry Third Edition Chapter 11 Enzymatic Catalysis Chapter 11 Enzymatic Catalysis Copyright © 2008 by John Wiley & Sons, Inc. Donald Voet Judith G. Voet Charlotte W. Pratt

2 Section 4 – Lysozyme NAG = N-acetylglucosamine NAM = N-acetylmuramic acid

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6 Asp – normal pK R = 3.09 Non-polar environment Glu – pK R = much higher than 4.07

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12 Transition state analog

13 Covalent catalysis

14 Section 5 – Serine Proteases Highly reactive serine Many digestive enzymes use this mechanism Inhibiting serine proteases can be very toxic

15 Identifying the active site residues Serine was identified by chemical labeling

16 His was identified by affinity labeling

17 Trypsin with leupeptin inhibitor Chymotrypsin Elastase also have similar Structures Asp is very important Catalytic triad Asp, His, Ser

18 Substrate Specificity

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25 Figure 11-30a

26 Figure 11-30b

27 Zymogens – inactive enzyme precursors

28 Fundamentals of Biochemistry Third Edition Fundamentals of Biochemistry Third Edition Chapter 12 Enzyme Kinetics, Inhibition, and Control Chapter 12 Enzyme Kinetics, Inhibition, and Control Copyright © 2008 by John Wiley & Sons, Inc. Donald Voet Judith G. Voet Charlotte W. Pratt

29 Section 3 – Control of Enzyme Activity Allosteric regulation

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31 T-state R-state

32 Figure 12-13

33 Covalent Modifications Phosphorylation is most common Ubiquitination important for protein degradation

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35 Glycogen Phosphorylase

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38 Penicillin Penicillin – 1928 Alexander Fleming Disrupts synthesis of peptidoglycans by transpeptidase –Used for bacterial cell walls Lactam ring is highly reactive

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40 Types of Penicillin First, injection only Acid stable, orally Most widely used

41 Mechanism of Penicillin

42 Bacterial Evolution Bacterial now produce an enzyme lactamase Inactivates penicillin

43 Human response Create inhibitor of β-lactamase Clavulanic acid Augmentin – combination of both amoxicillin and clavulanic acid New bateria resistant to both The battle continues…..

44 HIV Retrovirus – RNA genome Make a polyprotein consisting of 3 proteins –Reverse transcriptase, integrase, protease –Drugs for all enzymes –Drugs for attachment

45 Protease mechanisms Serine proteases (chymotrypsin) Cysteine proteases Aspartyl proteases (HIV protease) Metalloproteases

46 HIV protease mechanism

47 HIV protease inhibitors OH – mimics stable intermediate, benzene ring mimics hydrophobic aa

48 Other HIV drug targets Integrase inhibitors –FDA approved in 2007 (raltegravir) –Inhibits strand transfer of viral DNA into host genome Reverse Transcriptase Inhibitors –AZT 1987 –Nucleoside inhibitors (terminate DNA chain) –Non-nucleoside inhibitors (irreveribily bind to RT) Coming soon… –Viral fusion, maturation

49 HIV T-cell – green HIV – red


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