1. Chapter 6
Protein Function

2. 6.1 The Five Major Functional Classes of Proteins
Metabolism
Structure
Transport
Cell signaling
Genomic caretaker
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3. Protein Classifications by Function
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4. Copyright © 2017 W. W. Norton & Company
Metabolic Enzymes
Reaction catalysts that control metabolic flux
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5. Malate Dehydrogenase: A Metabolic Enzyme
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6. Copyright © 2017 W. W. Norton & Company
Structural Proteins
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7. Cytoskeletal Proteins: Examples of Structural Proteins
Structural proteins that are responsible for cell shape, cell migration, and cell signaling
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8. Actin: A Structural Protein
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9. Tubulin: A Structural Protein
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10. Collagen: A Structural Protein
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11. 6.2 Globular Transport Proteins: Oxygen Transport
Myoglobin
Hemoglobin
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12. Copyright © 2017 W. W. Norton & Company
Heme
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13. Myoglobin and Hemoglobin
Hemoglobin: Single polypeptide chain with one heme group
Myoglobin: Four polypeptides with two alpha and two beta subunits
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14. Regulation of Hemoglobin
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15. Copyright © 2017 W. W. Norton & Company
Heme Binding, Part 1
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16. Copyright © 2017 W. W. Norton & Company
Heme Binding, Part 2
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17. T and R State Conformations
T (tense) state
Oxygen is unbound (deoxyhemoglobin).
R (relaxed) state
Bound oxygen (oxyhemoglobin)
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18. Helical Representation of T  R Conversion
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19. Concerted and Sequential Models
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20. Fractional Saturation: θ
The fraction of protein binding sites that are occupied
[P] = concentration of protein
[L] = concentration of ligand
[PL] = concentration of protein-ligand complex
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21. Dissociation Constant: Kd
Reaction in which the dissociated species is the product
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22. Plot of Fractional Saturation
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23. Oxygen Binding Curves for Myoglobin and Hemoglobin
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24. Oxygen-Binding Properties of Hemoglobin
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25. Features of Ligand-Protein Interactions
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26. Copyright © 2017 W. W. Norton & Company
Bohr Effect
The pH and CO2 dependence of oxygen binding
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27. Hemoglobin and 2,3-Bisphosphoglycerate (2,3-BPG)
Found in red blood cells
Traps hemoglobin in the T state and acts as a negative effector
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28. Copyright © 2017 W. W. Norton & Company
2,3-BPG Binding
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29. Maternal Oxygen Transport to Fetus
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30. Copyright © 2017 W. W. Norton & Company
Anemia, Part 1
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31. Copyright © 2017 W. W. Norton & Company
Anemia, Part 2
Globin disease in the beta subunit
Genotype
Phenotype
Hemoglobin S (sickle cell)
Glu6 (A3) replaced by Val6
Globin protein aggregation
Hemoglobin Hammersmith
Phe42 (CD1) replaced by Ser42
Loss of heme binding
Hemoglobin Savannah
Gly24 (B6) replaced by Val24
Protein misfolding
Hemoglobin Milwaukee
Val67 (E11) replaced by Glu67
Loss of upper O 2 transport function
Hemoglobin Kansas
Asn102 (G4) replaced by Thr102
Destabilizes R state
Hemoglobin Yakima
Asp99 (G1) replaced by His99
Destabilizes T state
Globin disease in the alpha subunit
Genotype
Phenotype
Hemoglobin Bibba
Leu136 (H19) replaced by Pro136
Destabilizes tetramer
Hemoglobin St. Lukes
Pro95 (G2) replaced by Arg95
Hemoglobin Philadelphia
Tyr35 (C1) replaced by Phe35
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32. Copyright © 2017 W. W. Norton & Company
Sickle Cell Anemia
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33. 6.4 Structural Proteins: The Actin—Myosin Motor
It all started with the sliding filament model.
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34. Structure of Muscle Cells
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35. Copyright © 2017 W. W. Norton & Company
Muscle Cells
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36. Copyright © 2017 W. W. Norton & Company
Myosin and Actin
Myosin
Actin
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37. Copyright © 2017 W. W. Norton & Company
Filament Schematic
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38. Sliding Filament Model
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39. Muscle Contraction Mechanism
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40. Calcium Control and Muscle Contraction
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41. Copyright © 2017 W. W. Norton & Company
Muscle Contraction
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