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Fundamentals of Biochemistry

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

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




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






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







25 Figure 11-30a

26 Figure 11-30b

27 Zymogens – inactive enzyme precursors

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

29 Section 3 – Control of Enzyme Activity
Allosteric regulation


31 T-state R-state

32 Figure 12-13

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


35 Glycogen Phosphorylase



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


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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