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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 3:45 pm….Be there!!!. Many conformational states. Fewer conformational states. See VVP Fig 6-37 p153. A “single” conformational state. “Ideal”.
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Seminar W 4 pm BI 234 Dr. K. Cude!! A novel NFb pathway in the regulation of theG2/M phase of the cell cycle Refreshments at 3:45 pm….Be there!!!
Many conformational states Fewer conformational states See VVP Fig 6-37 p153 A “single” conformational state
“Ideal” “Real” ? See VVP Fig 6-38 p154
High energy Many conformational states Fewer conformational states (Fig 6-38) A “single” conformational state Low energy
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)
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.
Exploring collagen http://www.rcsb.org/pdb/molecules/pdb4_1.html
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.
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
Figure 8-63 The quaternary structure of hemoglobin. Page 266
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 ----------------------------> ATP + CO2 oxidative phosphorylation
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
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 ----------------------------> ATP + CO2 oxidative phosphorylation
Oxygen is transported down a concentration gradient pO2 torr
Transport of O , CO , H + 2 2 See VVP Fig 7-13 p173 lungs BPG.CO . Hb + 4O <===> Hb.(O ) + CO + BPG H . H + + + BPG.CO . Hb + 4O <===> Hb.(O ) + CO + BPG H . H + + + 2 2 2 4 2 2 2 2 4 2 O CO H , + 2 2 tissues Hb.(O ) + CO + BPG <===> BPG.CO . Hb + 4O H + H . + + Hb.(O ) + CO + BPG <===> BPG.CO . Hb + 4O H + H . + + 2 4 2 2 2 2 4 2 2 2 muscle cell membrane Mb O <===> Mb.O + Mb O <===> Mb.O + 2 2 2 2 mitochondria Mb.O <===> Mb O + Mb.O <===> Mb O + 2 2 2 2
VVP Fig 7-1
VVP Fig 7-3 heme myoglobin proximal His (bound to Fe)
VVP Fig 7-2 “proximal His”
P50 = 2.8 torr VVP Fig 7-4
Fraction of Mb bound to O2 at pO2 = 30 torr pO2 in capillaries P50 = 2.8 torr
myoglobin = single subunit hemoglobin = four homologous subunits: two alpha; two beta chains
Deoxy-Hb “T State” Oxy-Hb “R State” VVP Fig 7-5
VVP Fig7-7 Take Note p 65 Non-cooperative binding Cooperative binding
VVP Fig7-7 Take Note p 65 About 33% of O2 delivered
VVP Fig7-7 Take Note p 65 About 42% of O2 delivered
VVP Fig 7-9
4O2 + Hb-BPG-CO2-H+ Hb-(O2)4+ BPG + CO2 +H+ BPG + CO2 +H+ + Hb-(O2)4 Hb-BPG-CO2-H++ 4O2 O2 +Mb Mb-O2 Binding and Release of: O2, BPG, CO2, H+ See VVP Fig 7-13 Lungs: Capillaries: CO2 Respiring cells: Mitochondrion(O2) + Mb
VVP Fig. 7-14 Take Note p 69
Take Note p 69
Take Note p 68
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
How does this affect pKa for b H146? pKa for b H146increases, the protonated state is now favored. b H146 b D94 NH CO
Take Note p 378 VVP Fig 27-7
Ser Ser