Lecture 7 Fall 2009Chapter 8 :Globular ProteinsProtein StabilityQuaternary StructureChapter 9Protein FoldingAccessory FactorsPredicting Protein StructuresProtein DynamicsChapter 8Three Dimensional Three Dimensional Structure of Proteins(continued)Figure 8-35 X-Ray diffraction photograph of a single crystal of sperm whale myoglobin.Page 240X-Ray Crystallography and NMR• Dr. Robertus and Dr. Hoffman will cover these topics later in the semesterFigure 8-39a Representations of the X-ray structure of sperm whale myoglobin. (a) The protein and its bound heme are drawn in stick form.Globular ProteinsPage 244Figure 8-39b Representations of the X-ray structure of sperm whale myoglobin. (b) A diagram in which the protein is represented by its computer-generated Cαbackbone.Page 244Figure 8-39cRepresentations of the X-ray structure of sperm whale myoglobin. (c) A computer-generated cartoon drawing in an orientation similar to that of Part b.Page 244Figure 8-42aThe X-Ray structure of horse heart cytochrome.Page 246Hydrophobic side chains in redFigure 8-42bThe X-Ray structure of horse heart cytochrome.Page 246Hydrophilic side chains in greenThe bottom line is that the side chain location depends on the polarity of the side chain.Non-polar inside : Val,Leu, Ile, Phe, MetPolar outside : Arg, His, Lys, Glu, AspPolar outside : Arg, His, Lys, Glu, AspUncharged most often on surface: Ser,Thr, Asn, GLN, TyrFigure 8-43aThe H helix of sperm whale myoglobin. (a) A helical wheel representation in which the side chain positions about the α helix are projected down the helix axis onto a plane.Page 247Figure 8-43b The H helix of sperm whale myoglobin.(b) A skeletal model, viewed as in Part a.Page 247Figure 8-43c The H helix of sperm whale myoglobin.(c) A space-filling model, viewed from the bottom of the page in Parts a and b and colored as in Part b.Page 247Figure 8-48 The immunoglobulin fold.Page 251Read pages 248-255 re domainsProteins That Have The Immunoglobulin Fold• Serum Immunoglobulins•Cell Surface Immunoglobulins•Cell Surface Immunoglobulins• T-Cell ReceptorsFamilies of Protein Structural ElementsExamplesImmunoglobulin foldImmunoglobulin foldNAD binding domainRetinol binding domainFigure 8-45 DOMAINS One subunit of the enzyme glyceraldehyde-3-phosphate dehydrogenase from Bacillus stearothermophilus.Page 248Table 8-4 (top) Structural Bioinformatics Websites (URLs).Page 256Table 8-4 (middle) Structural Bioinformatics Websites (URLs).Page 256Table 8-4 (bottom) Structural Bioinformatics Websites (URLs)Page 258Protein Stability• Electrostatic Forces• Hydrogen Bonding• Hydrophobic Forces• Disulfide Bonds• Read pages 258 -264 for details• Protein DenaturationFigure 8-56 A GRASP diagram of human growth hormone.Red= -veBlue = +veWhite = neutralPage 258Figure 8-57 Dipole-dipole interactions.Page 259Table 8-5 Thermodynamic Changes for Transferring Hydrocarbons from Water to Nonpolar Solvents at 25°C.Page 261Table 8-6 Hydropathy Scale for Amino Acid Side Chains.Page 263Figure 8-60 Hydropathic index plot for bovine chymotrypsinogen.Page 263Figure 8-61 Protein denaturation.Page 264Shape of curve indicates that folding is cooperativeFigure 8-58 The orientational preference of water molecules next to a nonpolar solute.Page 262The three dimensional structure of proteins containing multiple subunitsFigure 8-63 The quaternary structure of hemoglobin.Page 266Figure 8-66aX-Ray structure of glutamine synthetase from Salmonella typhimurium.Page 268Figure 8-66bX-Ray structure of glutamine synthetase from Salmonella typhimurium.Page 268Figure 8-67 A helical structure composed of a single kind of subunit.Page 268Figure 8-68 Cross-linking agents.Page 269Chapter 9Protein Dynamics and FoldingRenaturationDeterminants of foldingVoet Biochemistry 3e© 2004 John Wiley & Sons, Inc.Determinants of foldingAccessory proteinsDesigning proteins from scratchDynamicsVoet Biochemistry 3e© 2004 John Wiley & Sons, Inc.Voet Biochemistry 3e© 2004 John Wiley & Sons, Inc.Figure 9-2 Reductive denaturation and oxidative renaturation of RNase A.Page 277Voet Biochemistry 3e© 2004 John Wiley & Sons, Inc.Figure 9-3 Plausible mechanism for the thiol- or enzyme-catalyzed disulfide interchange reaction in a protein.Page 278Box 4-C (1) Protein misfolding.Figure 4.18 Model of protein folding.Voet Biochemistry 3e© 2004 John Wiley & Sons, Inc.Figure 9-4 Primary structure of porcine proinsulin.Page 278Voet Biochemistry 3e© 2004 John Wiley & Sons, Inc.Figure 9-6 NMR structure of protein GB1.Page 280Voet Biochemistry 3e© 2004 John Wiley & Sons, Inc.Figure 9-7 X-Ray structure of Rop protein, a homodimer of αα motifs that associate to form a 4-helix bundlePage 281Voet Biochemistry 3e© 2004 John Wiley & Sons, Inc.Figure 9-8 A stopped-flow device.Page 282Voet Biochemistry 3e© 2004 John Wiley & Sons, Inc.Figure 9-9 UV absorbance spectra of the three aromatic amino acids, phenylalanine, tryptophan, and tyrosine.Page 282Voet Biochemistry 3e© 2004 John Wiley & Sons, Inc.Figure 9-10 Circular dichroism (CD) spectra of polypeptides.Page 283Voet Biochemistry 3e© 2004 John Wiley & Sons, Inc.Figure 9-11a Folding funnels. (a) An idealized funnel landscape.Page 285Voet Biochemistry 3e© 2004 John Wiley & Sons, Inc.Figure 9-11b Folding funnels. (b) The Levinthal “golf course” landscape.Page 285Voet Biochemistry 3e© 2004 John Wiley & Sons, Inc.Figure 9-11c Folding funnels. (c) Classic folding landscape.Page 285Voet Biochemistry 3e© 2004 John Wiley & Sons, Inc.Figure 9-11d Folding funnels. (d) Rugged energy surface.Page 285Voet Biochemistry 3e© 2004 John Wiley & Sons, Inc.Figure 9-12 Polypeptide backbone and disulfide bonds of native BPTI.Page 286Voet Biochemistry 3e© 2004 John Wiley & Sons, Inc.Figure 9-13 Renaturation of BPTI.Page 287Voet Biochemistry 3e© 2004 John Wiley & Sons, Inc.Figure 9-14a Reactions catalyzed by protein disulfide isomerase (PDI). (a) Reduced PDI catalyzes the rearrangement of the non-native disulfide bonds.Page 288Voet Biochemistry 3e© 2004 John Wiley & Sons, Inc.Figure 9-14b Reactions catalyzed by protein disulfide isomerase (PDI). (b) The oxidized PDI-dependent synthesis of disulfide bonds in proteins.Page 288Accessory FactorsVoet Biochemistry 3e© 2004 John Wiley & Sons, Inc.Figure 9-16 Electron micrograph-derived 3D image of the Hsp60 chaperonin from the photosynthetic bacterium Rhodobacter sphaeroides.Page 291Voet Biochemistry 3e© 2004 John Wiley & Sons, Inc.Figure 9-17a X-Ray structure of GroEL.