63
Vaccine War http:// www.pbs.org/wgbh/pages/frontline/vaccines / “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm in SL120

Vaccine War “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

  • View
    213

  • Download
    0

Embed Size (px)

Citation preview

Page 1: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Vaccine War

http://www.pbs.org/wgbh/pages/frontline/vaccines/

“Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm in SL120

Page 2: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

•SEMINARS!!!!

The Weiss Laboratory pursues both chemical and biological aspects of chemical biology. Using chemistry to advance a molecular understanding of biology, the lab dissects key events in biology with exceptionally diverse combinatorial libraries as atomic-scale scalpels. Our libraries, collections of different molecules, include virus-displayed proteins and chemically or enzymatically synthesized small molecules. Libraries displayed on the surfaces of viruses also offer essentially universal molecular recognition for chemical sensors, illustrating how biology can advance chemistry.

Prof. Gregory Weiss, Department of Chemistry, University of California, Irvine

Page 3: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Works exactly like HK.

Activated by [AMP] even in the presence of hi [ATP].

Inhibited by hi [ATP]or citrate

Page 5: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Figure 17-8 Mechanism for base-catalyzed aldol cleavage.

Pag

e 58

9

Transition state analogs like 2-phosphoglycolate inhibit the enzyme

CH2OP

OO_

Page 6: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Figure 17-9 Enzymatic

mechanism of Class I aldolase.

Pag

e 59

0

Page 7: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

OH

NHH

CH2OP

14Lys

Enzyme-Substrate Complex trapped by reduction of DHAP with NaBH4 followed by hydrolysis

Page 8: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Figure 16-10 Mechanism of aldose–ketose isomerization.

Pag

e 55

7

Page 9: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm
Page 10: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm
Page 11: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm
Page 12: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm
Page 13: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm
Page 14: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm
Page 15: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm
Page 16: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm
Page 17: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm
Page 18: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm
Page 19: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Figure 17-10 Proposed enzymatic mechanism of the TPI reaction: General Acid Catalysis.

pKs = 6.5 and 9.5Like PGIBut pK1 is for GLU! Normal pk?

GluAsp activity by 1000!

Reaction rate is diffusion limited!!

4.1

Page 20: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

End of Glycolysis Collection Phase

• Net result so far?– ATP– NAD+

– Carbon

Page 21: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Start of energy producing phase of glycolysis: Production of the first hi energy molecule.

Page 22: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Figure 17-13a Some reactions employed in elucidating the enzymatic mechanism of GAPDH. (a) The reaction of iodoacetate with an active site Cys residue. (b) Quantitative tritium transfer from substrate to NAD+.

Pag

e 59

6

32Pi also incorporated

Page 24: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm
Page 25: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm
Page 26: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm
Page 27: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm
Page 28: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm
Page 29: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm
Page 30: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Figure 17-14 Enzymatic mechanism of glyceraldehyde-3 phosphate dehydrogenase.

Pag

e 59

6 Go’ = +6.7 kJ!

Page 31: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm
Page 32: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Figure 17-15 Space-filling model of yeast phosphoglycerate kinase showing its deeply

clefted bilobal structure.

Pag

e 59

7

Page 33: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Figure 17-16 Mechanism of the PGK reaction.P

age

597

Go’ = -49.4 kJ! Go’ = -12.1 kJ

Page 34: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm
Page 36: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Figure 17-19 The pathway for the synthesis and degradation of 2,3-BPG in erythrocytes is a detour

from the glycolytic pathway.

Pag

e 60

0

Page 37: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Figure 17-20 The oxygen-saturation curves of hemoglobin (red) in normal

erythrocytes and those from patients with hexokinase (green) and pyruvate kinase

deficiencies (purple).

Pag

e 60

0

BPG

BPG

Page 38: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm
Page 39: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm
Page 40: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm
Page 41: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Figure 17-18

Proposed reaction

mechanism for

phospho-glycerate mutase.

Pag

e 59

9

Phosphorylatedactive site

Bisphospho-intermediate.

Page 42: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm
Page 43: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm
Page 44: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Figure 17-22 Mechanism of the reaction catalyzed by

pyruvate kinase.

Page 45: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm
Page 46: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Let's sing!!

• http://www.csulb.edu/~cohlberg/songbook.html

Page 47: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Lyrics

http://books.google.com/books?id=oq9ENyL_d9YC&lpg=PP1&pg=PA1#v=onepage&q&f=false

Page 48: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Figure 17-21 Proposed reaction mechanism of enolase.

Pag

e 60

1

F- binds Pi + Mg+2

Potent inhibitor

Page 49: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Figure 17-23 The active site region of porcine H4 LDH in complex with S-lac-NAD+, a

covalent adduct of lactate and NAD+.

Pag

e 60

3

Page 50: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Figure 17-24 Reaction mechanism of lactate dehydrogenase.

Pag

e 60

3

Page 51: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Figure 17-25 The two reactions of alcoholic

fermentation.

Pag

e 60

4

Page 52: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Figure 17-26 Thiamine pyrophosphate.

Pag

e 60

4

Page 53: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Figure 17-27

Reaction mechanism of pyruvate

decarboxylase.

Pag

e 60

5

Page 54: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Figure 17-29 The formation of the active ylid form of TPP in the

pyruvate decarboxylase

reaction.

Pag

e 60

6

Page 55: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Figure 17-30The reaction mechanism of alcohol dehydrogenase involves direct hydride transfer of the pro-R hydrogen of NADH to the re face of acetaldehyde.

Pag

e 60

6

Page 56: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Table 17-2 Some Effectors of the Nonequilibrium Enzymes of Glycolysis.

Pag

e 61

3

Page 57: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Figure 17-32a X-Ray structure of PFK. (a) A ribbon diagram showing two subunits of the

tetrameric E. coli protein.

Pag

e 61

4

Mg+2

ATP

F6P

Page 58: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Figure 17-33 PFK activity versus F6P concentration.

Pag

e 61

5

Page 59: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Figure 17-35 Metabolism of fructose.

Pag

e 61

9

Page 60: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Figure 17-36 Metabolism of galactose.

Pag

e 62

1

Page 61: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Figure 17-37 Metabolism of mannose.

Pag

e 62

1

Page 62: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

Figure 17-31 Schematic diagram of the plasmid constructed to control the amount of

citrate synthase produced by E. coli.

Pag

e 60

9

Page 63: Vaccine War  “Undergraduate Research Opportunities” will be held Today, Thursday, Jan 13, at 3:30 pm

“Alfonse, Biochemistry makes my head hurt!!”\