Slide 1:Chapter 04 Peptides and Proteins


Slide 2:Formation of a Peptide Bond Between Two Amino Acids The result is a dipeptide named alanylserine


Slide 3:The pentapeptide serylglycyltyrosylalanylleucine, Ser–Gly–Tyr–Ala–Leu, or SGYAL.


Slide 4:Alanylglutamylglycyllysine and its ionizable groups


Slide 5:Aspartame (aspartylphenylalanine methyl ester).


Slide 6:Molecular Data on Some Proteins


Slide 7:Amino Acid Composition of Two Proteins


Slide 8:Conjugated Proteins


Slide 9:A molecule of glycine (blue) and chymotrypsin is shown for size comparison Proteins in any of their functional, folded conformations are called native proteins


Slide 10:Primary Structure


Slide 11:Secondary structure


Slide 12:Tertiary structure


Slide 13:Quaternary structure


Slide 14:Structure of a Protein


Slide 16:Bovine (Bos taurus) ribonuclease A.


Slide 17:Bovine ribonuclease A NMR structure.


Slide 18:Resonance structure of the peptide bond.


Slide 20:Linus Pauling Robert Corey Corey and Pauling proposed a planar peptide bond


Slide 21:Planar peptide groups in a polypeptide chain. A peptide group consists of the N—H and C=C groups involved in formation of the peptide bond, as well as the -carbons on each side of the peptide bond.


Slide 22:Three bonds separate sequential α carbons in a polypeptide chain. The N—Cα and Cα—C bonds can rotate, described by dihedral angles designated Φ and Ψ, respectively. The peptide C—N bond is not free to rotate. Other single bonds in the backbone may also be rotationally hindered, depending on the size and charge of the R groups.


Slide 25:A region of -helical secondary structure is shown with the N-terminus at the bottom and the C-terminus at the top of the figure. Pitch and Rise of the Helix In a right-handed helix, the backbone turns in a clockwise direction when viewed along the axis from its N-terminus.


Slide 27:Propensity of Amino Acids to Take Up an α-Helical Conformation


Slide 32:View of a right-handed  helix. (horse liver alcohol dehydrogenase) The blue ribbon indicates the shape of the polypeptide backbone. All the side chains, shown as ball-and- stick models, project outward from the helix axis.


Slide 33:Sequence of amino acids of horse liver alcohol dehydrogenase Highly hydrophobic residues are blue, less hydrophobic residues are green, and highly hydrophilic residues are red. Helical wheel diagram.


Slide 34:The amphipathic  helix is highlighted. The side chains of highly hydrophobic residues are shown in blue, less hydrophobic residues are green, and charged residues are shown in red. The side chains of the hydrophobic residues are directed toward the interior of the protein and that the side chains of charged residues are exposed to the surface.


Slide 35:Leucine zipper region of yeast (Saccharomyces cerevisiae) protein bound to DNA. GCN4 is a transcription regulatory protein that binds to specific DNA sequences. The DNA-binding region consists of two amphipathic helices, one from each of the two subunits of the protein. The side chains of leucine residues are shown in a darker blue than the ribbon.


Slide 36:These top and side views reveal the R groups extending out from the β sheet and emphasize the pleated shape described by the planes of the peptide bonds. (An alternative name for this structure is β-pleated sheet.) Hydrogen-bond cross-links between adjacent chains are also shown. The amino-terminal to carboxyl-terminal orientations of adjacent chains (arrows) can be the same or opposite


Slide 37:Parallel  Sheets. The hydrogen bonds are evenly spaced but slanted. (Arrows indicate the N- to C-terminal direction of the peptide chain. )


Slide 38:Antiparallel  sheet. The hydrogen bonds are essentially perpendicular to the  strands, and the space between hydrogen-bonded pairs is alternately wide and narrow.


Slide 39:View of two strands of an antiparallel  sheet from influenza virus A neuraminidase. Only the side chains of the front  strand are shown. The side chains alternate from one side of the  strand to the other side. Both strands have a right-handed twist.


Slide 40:Structure of PHL P2 from Timothy grass (Phleum pratense) pollen The two short two-stranded antiparallel  sheets are highlighted in blue and purple to show their orientation within the protein


Slide 41:Structure of PHL P2 from Timothy grass (Phleum pratense) pollen View of the -sandwich structure in a different orientation showing hydrophobic residues (blue) and polar residues (red). A number of hydrophobic interactions connect the two  sheets.


Slide 42:Structures of β turns. Type I and type II β turns are most common Type I turns occur more than twice as frequently as type II. Type II β turns usually have Gly as the third residue. Note the hydrogen bond between the peptide groups of the first and fourth residues of the bends.


Slide 46:TRUE


Slide 47:Common Motifs. In folded proteins  helices and  strands are commonly connected by loops and turns to form supersecondary structures. Arrows indicate the N- to C-terminal direction of the peptide chain.


Slide 48:Pyruvate kinase from cat (Felis domesticus) The main polypeptide chain of this common enzyme folds into three distinct domains as indicated by brackets.


Slide 49:Different Cytochrome c. (a) Tuna (Thunnus alalunga) cytochrome c bound to heme (b) Tuna cytochrome c polypeptide chain. (c) Rice (Oryza sativa) cytochrome c (d) Yeast (Saccharomyces cerevisiae) cytochrome c (e) Bacterial (Rhodopila globiformis) cytochrome c


Slide 50:Structural similarity of lactate and malate dehydrogenase. (a) Bacillus stereothermophilus lactate dehydrogenase (b) Escherichia coli malate dehydrogenase


Slide 51:Brewer’s yeast (Saccharomyces carlsburgensis) old yellow enzyme (FMN oxidoreductase) (class: /). The central fold is an / barrel with parallel  strands connected by  helices. Two of the connecting -helical regions are highlighted in yellow.


Slide 52:Escherichia coli enzyme required for tryptophan biosynthesis (class: /). This is a bifunctional enzyme containing two distinct domains. Each domain is an example of an / barrel. The left-hand domain contains the indolglycerol phosphate synthetase activity, and the right-hand domain contains the phosphoribosylanthranilate isomerase activity.


Slide 53:Pig (Sus scrofa) adenylyl kinase (class: /). This single-domain protein consists of a five-stranded parallel  sheet with layers of  helices above and below the sheet. The substrate binds in the prominent groove between a helices.


Slide 54:Escherichia coli flavodoxin (class: /). The fold is a five-stranded parallel twisted sheet surrounded by  helices.


Slide 55:Human (Homo sapiens) thioredoxin (class: /). The structure of this protein is very similar to that of E. coli flavodoxin except that the five-stranded twisted sheet in the thioredoxin fold contains a single antiparallel strand.


Slide 56:Escherichia coli L-arabinose-binding protein (class: /). This is a two-domain protein where each domain is similar to that in E. coli flavodoxin. The sugar L-arabinose binds in the cavity between the two domains.


Slide 57:Escherichia coli DsbA (thiol-disulfide oxidoreductase/ disulfide isomerase) (class: /). The predominant feature of this structure is a (mostly) antiparallel  sheet sandwiched between helices. Cysteine side chains at the end of one of the  helices are shown (sulfur atoms are yellow).


Slide 58:Neisseria gonorrhea pilin (class:  + ). This polypeptide is one of the subunits of the pili on the surface of the bacteria responsible for gonorrhea. There are two distinct regions of the structure: a  sheet and a long a helix.


Slide 59:Common domain folds.


Slide 60:A simple motif, the β-α-β loop.


Slide 61:Stable folding patterns in proteins. (a) Connections between β strands in layered β sheets. The strands here are viewed from one end, with no twisting. Thick lines represent connections at the ends nearest the viewer; thin lines are connections at the far ends of the β strands. The connections at a given end (e.g., near the viewer) do not cross one other. (b) Because of the right-handed twist in β strands, connections between strands are generally right-handed. Left-handed connections must traverse sharper angles and are harder to form. (c) This twisted β sheet is from a domain of photolyase (a protein that repairs certain types of DNA damage) from E. coli (derived from PDB ID 1DNP). Connecting loops have been removed so as to focus on the folding of the β sheet.


Slide 62:Constructing large motifs from smaller ones. The α/β barrel is a commonly occurring motif constructed from repetitions of the α-β-α loop motif. This α/β barrel is a domain of pyruvate kinase (a glycolytic enzyme) from rabbit


Slide 63:Organization of proteins based on motifs. Shown here are just a few of the hundreds of known stable motifs. They are divided into four classes: all α, all β, α/β, and α + β. Structural classification data from the SCOP (Structural Classification of Proteins) database The PDB identifier (listed first for each structure) is the unique accession code given to each structure archived in the Protein Data Bank (www.rcsb.org).


Slide 64:Examples of tertiary structure in selected proteins Human (Homo sapiens) serum albumin (class: all-). This protein has several domains consisting of layered  helices and helix bundles


Slide 65:Escherichia coli cytochrome 562 (class: all-). This is a heme-binding protein consisting of a single four-helix bundle domain.


Slide 67:Escherichia coli UDP N-acetylglucosamine acyl transferase (class: all-). The structure of this enzyme shows a classic example of a -helix domain.


Slide 68:Jack bean (Canavalia ensiformis) concanavalin A This carbohydrate-binding protein (lectin) is a single-domain protein made up of a large -sandwich fold


Slide 69:Human (Homo sapiens) peptidylprolyl cis/trans isomerase (class: all-). The dominant feature of the structure is a -sandwich fold.


Slide 70:Jellyfish (Aequorea victoria) green fluorescent protein (class: all-) This is a -barrel structure with a central  helix. The strands of the sheet are antiparallel.


Slide 71:This β barrel is a single domain of α-hemolysin (a toxin that kills a cell by creating a hole in its membrane) from the bacterium Staphylococcus aureus .


Slide 74:Pig (Sus scrofa) retinol-binding protein (class: all-). Retinol binds in the interior of a -barrel fold.


Slide 75:Examples of Quaternary structures. Chicken (Gallus gallus) triose phosphate isomerase. This protein has two identical subunits with / barrel folds


Slide 76:HIV-1 aspartic protease This protein has two identical all- subunits that bind symmetrically. HIV protease is the target of many new drugs designed to treat AIDS patients.


Slide 77:Streptomyces lividans potassium channel protein This membrane-bound protein has four identical subunits, each of which contributes to a membrane-spanning eight-helix bundle.


Slide 78:Bacteriophage MS2 capsid protein. The basic unit of the MS2 capsid is a trimer of identical subunits with a large  sheet.


Slide 79:Human (Homo sapiens) hypoxanthine-guanine phosphoribosyl transferase (HGPRT). HGPRT is a tetrameric protein containing two different types of subunit.


Slide 80:Rhodopseudomonas viridis photosystem This complex, membrane-bound protein has two identical subunits (orange, blue) and two other subunits (purple, green) bound to several molecules of photosynthetic pigments.


Slide 81:FIBROUS vs. GLOBULAR PROTEINS


Slide 82:Collagen is the most abundant protein in the human body. It is the cementing component of various connective tissues like bones, tendons, ligaments, and skin.


Slide 83:(a) The α-chain of collagen has a repeating secondary structure unique to this protein. (b) Space-filling model of the same α chain. (c) Three of these helices (shown here in gray, dark blue, and light blue) wrap around one another with a right-handed twist. (d) The three-stranded collagen superhelix shown from one end. Gly residues are shown in red.


Slide 84:The structure of collagen can be likened to a rope. The primary structure of collagen is a repeating sequence of –Gly-X-Y- where X is usually proline and Y is 4-hydroxyproline or lysine Glycine is the amino acid that is located at the overlapping regions of the three α-helices because it is the only amino acid that is small enough to fit through these tight regions. Proline renders rigidity to the structure while 4-hydroxyproline forms H-bonds that further strengthen the fiber. In addition, some lysine residues are present and oxidized into aldehyde groups that cross-link with one another.


Slide 85:Collagen is a rod-shaped molecule, about 3,000 Å long and only 15 Å thick. Its three helically intertwined α chains may have different sequences; each chain has about 1,000 amino acid residues. Collagen fibrils are made up of collagen molecules aligned in a staggered fashion and cross-linked for strength.


Slide 87:Vitamin C (ascorbic acid) is needed to maintain the structural integrity of collagen. It is required in the hydroxylation of proline to 4-hdroxyproline. Proline 4-Hydroxyproline


Slide 88:Ascorbic acid is a water soluble vitamin that is not stored in the body, hence recommended daily intake of this vitamin is up to 500 mg.


Slide 89:Prolonged deficiency results to scurvy which is characterized by swelling & inflammation of gums, impaired healing of wounds, loosening of the teeth, pain in joints, and progressive weakening of the body.


Slide 91:Alpha keratin is the major protein in hair & nails, and a minor constituent of the skin. It is also a component of the cells cytoskeleton that maintains their shape.


Slide 92:Alpha keratin is made up of two α-helices that are twisted together to form a left-handed super helix. These then combine in higher-order structures called protofilaments and protofibrils. About four protofibrils—32 strands of α -keratin in all—combine to form an intermediate filament. Eight protofibrils combine in a circular or square arrangement to form a microfibril in hair and nails respectively


Slide 93:A hair is an array of many α-keratin filaments, made up of the substructures shown Keratin is further strengthened by the formation of disulfide bridges by cysteine residues.


Slide 94:In the perming of the hair, the disulfide bonds are broken by a perming solution. The waves and curls are then set by rollers and after sometime a neutralizing solution is added to reform the disulfide bonds. This results to the formation of permanent waves and curls. The same principle is applied in hair straightening. Now that’s the Biochemistry for a new hairdo!


Slide 95:Hair α -keratin is an elongated α helix with somewhat thicker elements near the amino and carboxyl termini. Pairs of these helices are interwound in a left-handed sense to form two-chain coiled coils. These then combine in higher-order structures called protofilaments and protofibrils. About four protofibrils—32 strands of α -keratin in all—combine to form an intermediate filament. The individual two-chain coiled coils in the various substructures also seem to be interwound, but the handedness of the interwinding and other structural details are unknown.


Slide 96:ALPHA KERATIN Structure


Slide 97:Silk fibroins are the fibers formed by silkworms & spiders. It is made up of anti-parallel α-pleated sheets with the amino acid sequence of –Gly-X- where X is either alanine or serine. Strands of fibroin (blue) emerge from the spinnerets of a spider in this colorized electron micrograph.


Slide 98:Silk is woven into a smooth and elegantly lustrous textile. Silk is tough along the axis of the amino acid chain but very flexible in the lateral regions that are solely stabilized by H-bonds.


Slide 99:Similar to collagen, glycine fits through the tight regions between the chains.


Slide 101:If globular human serum albumin are stretched into a α helix or β conformation


Slide 102:Myoglobin is the carrier of oxygen in the muscles. It is made up of a four subunits which are designated as 1, 2, 1, and 2. Each subunit is made up of a non-protein component or prosthetic group. This is the heme group which consists of a porphyrin ring with a coordinated Fe atom. The protein component is called globin which of course has a globular shape.


Slide 103:The heme group viewed from the side.


Slide 104:The polypeptide backbone in a ribbon representation. The α-helical regions are evident. (The heme group is shown in red.) Surface contour image; this is useful for visualizing pockets in the protein where other molecules might bind. Ribbon representation including side chains (blue) for the hydrophobic residues Leu, Ile, Val, and Phe. Space-filling model with all amino acid side chains


Slide 105:Hemoglobin is the carrier of oxygen in the blood. It is a tetrameric protein wherein each monomer is made up of a four subunits just like in myoglobin. The form of hemoglobin that is without is known as deoxyhemoglobin. The iron atom of the heme group binds oxygen to form oxyhemoglobin.


Slide 106:A distal and proximal histidine residues stabilize the binding of oxygen to heme group.


Slide 108:Anemia are disorders that result from deficiency and alteration in the structure of hemoglobin or the number of RBCs.


Slide 109:Iron deficiency anemia (IDA) results from inadequate supply of iron in the body due to malnutrition or malabsorption of the mineral. The RBCs become distinctively smaller in size (microcytis).


Slide 110:Folate is a B-vitamin that is needed in the synthesis of hemoglobin. Deficiency in folate leads to megaloblastic anemia characterized by large immature RBCs. A form of megaloblastic anemia is caused by a deficiency in vitamin B12 (cobalamin) which is specifically called as pernicious anemia.


Slide 111:Women lose iron during menstruation and pregnancy hence they may need more iron and folate supplementation.


Slide 112:Alterations in the structure of hemoglobin may result to life-threatening conditions. Sickle-cell anemia is the distortion of the RBCs into sickle shapes due to the precipitation of hemoglobin during the deoxygenated form. This results from a single point mutation where glutamic acid is substituted by valine in the sixth amino residue of the β subunit of hemoglobin.