Seminar W 4 pm BI 234

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Seminar W 4 pm BI 234 Dr. K. Cude!!
A novel NF?b pathway in the regulation of
theG2/M phase of the cell cycle
Refreshments at 345 pm.Be there!!!
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Many conformational states
Fewer conformational states
See VVP Fig 6-37 p153
A single conformational state
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Ideal
Real ?
See VVP Fig 6-38 p154
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High energy
Many conformational states
Fewer conformational states
(Fig 6-38)
A single conformational state
Low energy
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H-bond Fun Facts

• 1984 survey of protein crystal data shows that
  almost all groups capable of forming H-bonds do
  so. (mainchain amides, polar sidechains)

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VVP Fig 6-39 Take Note p 61
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Protein Explorer http//molvis.sdsc.edu/protexpl/
frntdoor.htm Do the 1 hour tour at this site.
http//molvis.sdsc.edu/protexpl/qtour.htm It may
take longer than 1 h.
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Mb
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Exploring collagen
http//www.rcsb.org/pdb/molecules/pdb4_1.html
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Globular Protein 3o Structure

• 2o structural elements (helices, sheets, turns)
  pack together to give a folded protein or
  subunit. This so-called tertiary structure is
  stabilized by non-covalent interactions, the
  hydrophobic effect and disulfides. Within the 3o
  structure are motifs and domains.
• The 3o structure can be derived from one or more
  domains.

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Structural features of most globular proteins
1. Very compact e.g. Mb has room for only4
water molecules in its interior.
2. Most polar/charged R groups are on the
surface and are hydrated.
3. Nearly all the hydrophobic R groups are on
the interior.
4. Pro occurs at bends/loops/random structures
and in sheets
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Figure 8-63 The quaternary structure of
hemoglobin.
Page 266
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Oxygen is transported to cells
which are remote from air

O2 is required in cells, in the mitochondria for
ATP production
aerobic metabolism
Glucose O2 ----------------------------gt ATP
CO2
oxidative phosphorylation
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Normal Red Blood Cells have a flattened discoid
shape rather than a spherical shape
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
vs.
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
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Oxygen is transported to cells
which are remote from air

O2 is required in cells, in the mitochondria for
ATP production
aerobic metabolism
Glucose O2 ----------------------------gt ATP
CO2
oxidative phosphorylation
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Oxygen is transported down
a concentration gradient
pO2
torr
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See VVP Fig 7-13 p173
lungs
BPG.CO
.
H
.
Hb 4O
ltgt Hb.(O
)

H

CO
BPG


BPG.CO
.
Hb 4O
ltgt Hb.(O
)

CO
BPG
H
.
H



2
2
2
4
2
2
2
2
4
2
O

H
,
CO

2
2
tissues
Hb.(O
)

CO
BPG ltgt BPG.CO
.
Hb 4O
H

H
.


Hb.(O
)

H

CO
BPG ltgt BPG.CO
.
H
.
Hb 4O


2
4
2
2
2
2
4
2
2
2
muscle cell membrane
Mb

O
ltgt Mb.O
Mb

O
ltgt Mb.O
2
2
2
2
mitochondria
Mb.O
ltgt Mb

O
Mb.O
ltgt Mb

O
2
2
2
2
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VVP Fig 7-1
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VVP Fig 7-3
heme
myoglobin
proximal His (bound to Fe)
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VVP Fig 7-2
proximal His
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P50 2.8 torr
VVP Fig 7-4
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Fraction of Mb bound to O2 at pO2 30 torr
pO2 in capillaries
P50 2.8 torr
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myoglobin single subunit
hemoglobin four homologous subunits two alpha
two beta chains
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VVP Fig 7-7
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VVP Fig 7-5a
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VVP Fig 7-5b
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Oxy-Hb R State
Deoxy-Hb T State
VVP Fig 7-5
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VVP Fig 7-7
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VVP Fig7-7 Take Note p 65
Non-cooperative binding
Cooperative binding
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VVP Fig7-7 Take Note p 65
About 33 of O2 delivered
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VVP Fig7-7 Take Note p 65
About 42 of O2 delivered
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VVP Fig 7-8
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VVP Fig 7-9
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VVP Fig 7-10
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Binding and Release of O2, BPG, CO2, H
See VVP Fig 7-13
Lungs
Capillaries
CO2
Respiring cells
Mitochondrion(O2) Mb
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VVP Fig. 7-14 Take Note p 69
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Take Note p 69
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Take Note p 68
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b H146 is deprotonated in the R state
b H146
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The R to T transition brings b D94 close to b
H146. How does this affect pKa for b H146?
b H146
b D94
NH
CO
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How does this affect pKa for b H146? pKa for b
H146 increases, the protonated state is now
favored.
b H146
b D94
NH
CO
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VVP Fig 7-15
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adaptation to high altitude increased BPG
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Take Note p 378 VVP Fig 27-7
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Like VVP Fig 7-15
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Normal Red Blood Cells
Sickled Red Blood Cells
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VVP Fig 7-17
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Hb A)
Normal hemoglobin (
deoxyhemoglobin
Oxy Hb A
T state
R state
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Sickle Hemoglobin (Hb S)
See VVP Fig 7-17
b E6V mutation on surface of Hb causes
aggregation of deoxy Hb
deoxy Hb S
Oxy Hb S
forms polymeric rods
in T state
R state
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Hemolysis of a Sickled Red Blood Cell
VVP Fig 7-18
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VVP Fig 7-19 Symmetry Model of Allosterism
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VVP Fig 7-20 The Sequential Model of Allosterism
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VVP Fig 7-32
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Antibody binding is highly specific

• How is this specificity mediated?
• Complementarity receptor/ligand binding is
  essentially pattern recognition between two
  complementary surfaces.

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Take Note p 75
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VVP Fig 7-33
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sheets are linked by a disulfide bond
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Fv
Fab
binding sites
Fc
IgG molecule
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Lysozyme-antibody Fab fragment complex
antigen
binding site
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VVP Fig 7-36