Lesk: Introduction to Protein Science 
Animated FiguresLesk: Introduction to Protein Science
Chapter 2
Genomics and Proteomics
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Fig 2-3: α-helices and β-sheets are two 'prefabricated' structures that appear in many proteins:
Fig 2-3a (α-helix) static, rotating
Fig 2-3b (parallel β-sheet) static, rotating
Fig 2-3c (antiparallel β-sheet) static, rotating
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Fig 2-4: Superposition of structures of histidine-containing phosphocarrier proteins from Escherichia coli (black) and Streptococcus faecalis (red). Although over 60% of the residues have mutated, the folding pattern is completely intact.static, rotating
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Fig 2-6a: The coiled-coil structure of á-keratin also appears in the eukaryotic transcriptional activator GCN4. This structure contains two helices coiled around each other. It is known as the 'leucine zipper' because of the leucine repeats every 7 residues (shown in ball-and-stick representation). The pitch is 14.7 nm. static, rotating
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Fig 2-7: The structure of collagen, a three-stranded supercoil formed by braiding together three polypeptide chains. In each strand, the rise per residue is approximately 0.3 nm. Each polypeptide chain itself forms a helix, with approximately 3.3 residues per turn. The repeat distance of the supercoil is approximately 1 nm static, rotating
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Fig 2-8: An enzyme-substrate complex: E. coli N-acetyl-L-glutamate kinase binding the substrate N-acetylglutamate and the inhibitory cofactor analogue AMPPNP (instead of the natural cofactor ATP). The substrate and inhibitor nestle snugly into the enzyme, which holds them in proper proximity for phosphate transfer. (a) The substrate and cofactor analogue occupy a crevice in the molecule. static, rotating (b) The mainchain and sidechains that surround the ligands. static, rotating
Fig 2-9: Simplified diagram of the energetics of a reaction. Typically substrates and products are stable species, as shown by their positions at local minima of the energy. To change substrate to product, the system must pass through intervening states of higher energy. The highest-energy peak in the trajectory is called the transition state. The height of this energy barrier determines the rate of reaction. To speed up reactions, enzymes can lower energy barriers by stabilizing transition states. In some cases, coupling of reactions to enzymes can provide alternative pathways of reaction, with lower transition-state energies. static
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Fig 2-10: Thrombin, a key player in the control of blood coagulation, is a member of the chymotrypsin family of serine proteinases. The active site lies in a cleft between two domains. The two domains are homologues, that arose by gene duplication and divergence. Human thrombin binds the synthetic inhibitor hirulog-3, a 20-residue peptide related to the natural inhibitor hirudin from the leech. Hirulog interacts with both the catalytic site and an anion-binding exosite specific to thrombin. static, rotating
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Fig 2-11: HIV-1 proteinase binds a stable macrocyclic inhibitor that mimics a tripeptide moiety of the natural substrate. (a) The proteinase is a homodimer, with a binding site shared between the monomers. (In order to show the ligand, the orientation is oblique to the axis of symmetry.) static, rotating
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Fig 2-12: Retinol-binding protein is an example of a β-barrel, in which the strands of a β-sheet are wrapped around into a cylinder, with continuous lateral hydrogen bonding around the circumference of the barrel. By forming barrels of different sizes, from different numbers of strands, proteins can create interior cavities of different sizes to bind different ligands. static rotating
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Fig 2-14: The structure of bacteriorhodopsin from Halobacterium salinarum illustrating the common theme of a 7-transmembrane helix structure static, rotating Bacteriorhodopsin is a light-driven pump, converting light energy absorbed by the chromophore, retinal, to a proton gradient across the membrane.
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Fig 2-3: á-helices and â-sheets are two 'prefabricated' structures that appear in many proteins:
Fig 2-3a (á-helix) static, rotating
Fig 2-3b (parallel â-sheet) static, rotating
Fig 2-3c (antiparallel â-sheet) static, rotating
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Fig 2-4: Superposition of structures of histidine-containing phosphocarrier proteins from Escherichia coli (black) and Streptococcus faecalis (red). Although over 60% of the residues have mutated, the folding pattern is completely intact.static, rotating
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Fig 2-6a: The coiled-coil structure of á-keratin also appears in the eukaryotic transcriptional activator GCN4. This structure contains two helices coiled around each other. It is known as the 'leucine zipper' because of the leucine repeats every 7 residues (shown in ball-and-stick representation). The pitch is 14.7 nm. static, rotating
Page 28:
Fig 2-7: The structure of collagen, a three-stranded supercoil formed by braiding together three polypeptide chains. In each strand, the rise per residue is approximately 0.3 nm. Each polypeptide chain itself forms a helix, with approximately 3.3 residues per turn. The repeat distance of the supercoil is approximately 1 nm static, rotating
Page 30:
Fig 2-8: An enzyme-substrate complex: E. coli N-acetyl-L-glutamate kinase binding the substrate N-acetylglutamate and the inhibitory cofactor analogue AMPPNP (instead of the natural cofactor ATP). The substrate and inhibitor nestle snugly into the enzyme, which holds them in proper proximity for phosphate transfer. (a) The substrate and cofactor analogue occupy a crevice in the molecule. static, rotating (b) The mainchain and sidechains that surround the ligands. static, rotating
Fig 2-9: Simplified diagram of the energetics of a reaction. Typically substrates and products are stable species, as shown by their positions at local minima of the energy. To change substrate to product, the system must pass through intervening states of higher energy. The highest-energy peak in the trajectory is called the transition state. The height of this energy barrier determines the rate of reaction. To speed up reactions, enzymes can lower energy barriers by stabilizing transition states. In some cases, coupling of reactions to enzymes can provide alternative pathways of reaction, with lower transition-state energies. static
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Fig 2-10: Thrombin, a key player in the control of blood coagulation, is a member of the chymotrypsin family of serine proteinases. The active site lies in a cleft between two domains. The two domains are homologues, that arose by gene duplication and divergence. Human thrombin binds the synthetic inhibitor hirulog-3, a 20-residue peptide related to the natural inhibitor hirudin from the leech. Hirulog interacts with both the catalytic site and an anion-binding exosite specific to thrombin. static, rotating
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Fig 2-11: HIV-1 proteinase binds a stable macrocyclic inhibitor that mimics a tripeptide moiety of the natural substrate. (a) The proteinase is a homodimer, with a binding site shared between the monomers. (In order to show the ligand, the orientation is oblique to the axis of symmetry.) static, rotating
Page 33:
Fig 2-12: Retinol-binding protein is an example of a β-barrel, in which the strands of a β-sheet are wrapped around into a cylinder, with continuous lateral hydrogen bonding around the circumference of the barrel. By forming barrels of different sizes, from different numbers of strands, proteins can create interior cavities of different sizes to bind different ligands. static rotating
Page 34:
Fig 2-14: The structure of bacteriorhodopsin from Halobacterium salinarum illustrating the common theme of a 7-transmembrane helix structure static, rotating Bacteriorhodopsin is a light-driven pump, converting light energy absorbed by the chromophore, retinal, to a proton gradient across the membrane.
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Fig 2-15: The structure of E. coli outer membrane protein A (ompa), a β-barrel protein traversing the cell membrane. Ompa appears in gram negative bacteria as a structural membrane protein interacting with lipoproteins, and also serves as a docking site for the bacteriocidal protein colicin, and some phages, and is also involved in conjugation. static, rotating
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Fig 2-17: Human growth hormone (blue) in complex with two molecules illustrating the dimerized exterior domain of its receptor static, rotating
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Fig 2-18: p21 Ras binding GTP static, rotating. Although an active GTPase the system was stabilized for crystal-structure analysis by cooling to 100 K.
Fig 2-19: The conformational change in p21 Ras from the inactive GDP-binding conformation to the active GTP-binding conformation primarily involves two regions (shown here in red), that form a patch on the molecular surface static, rotating
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Fig 2-20: Comparison of the folding patterns of two small proteins. (a) Cow acylphosphatase static, rotating (b) Viral toxin from corn smut fungus (Ustilago maydis) static, rotating Although there are many superficial similarities between the folding patterns of these two proteins, they have different topologies (unlike the two related proteins in Figure 2-4).
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Fig 2-22: Proteins from the globin family assemble different combinations of oligomers. (a) monomer: Sperm whale myoglobin static, rotating (b) dimer of two identical subunits: Ark clam globin static, rotating (c) mixed tetramer: Human haemoglobin containing two αchains and two βchains static, rotating
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Fig 2-23: Antibody molecule, illustrating both the concatenation of domains within each of the four chains, and the formation of a dimer. Like haemoglobin, this molecule is a dimer of dimers, containing two identical light chains and two identical heavy chains. The antigen-binding sites are at the 'wingtips'. static, rotating
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