Cellular Functions, Monomeric Units

OUTLINE Components of Life • Proteins – Definition – Size – Shape – Solubility – Stability • Types – Familiar – Structural – Functional • Ways of depicting Shape • Configuration vs. Conformation Review from Lecture 1: Components of Life Going to talk about each of these and discover for each: 1. cellular functions 2. monomeric units 3. name of the bond that makes the polymer 4. characteristics of the macromolecule in terms of shape Macromolecules in living organisms: proteins, carbohydrates, nucleic acids, “lipids”; nearly all are polymers Polymers are composed of smaller molecules called monomers, which are part of the precursors of the polymer • Proteins: combinations of 20 kinds of amino acid precursors • Polysaccharides: sugar monomers, called monosaccharides (many kinds), are combined. Both monomers and polymers are called Carbohydrates • Nucleic acids: combinations of 8 kinds of nucleotide precursors/monomers •[ Lipids: non-covalent forces maintain interactions between lipid monomers] Proteins What is the secret of life? “He said he hoped a lot of us would have careers in science,' she said. She didn't see anything funny in that. She was remembering a lesson that had impressed her. She was repeating it, gropingly, dutifully. 'He said, the trouble with the world was...’ 'The trouble with the world was,' she continued hesitatingly, 'that people were still superstitious instead of scientific. He said if everybody would study science more, there wouldn't be all the trouble there was.’ 'He said science was going to discover the basic secret of life some day,' the bartender put in. He scratched his head and frowned. 'Didn't I read in the paper the other day where they'd finally found out what it was?’ ― Kurt Vonnegut Jr., Cat's Cradle 11 Proteins Definition: Proteins are a linear polymers of L-a-amino acids. (generally composed of 20 different types) “L” refers to the old-style of configuration* nomenclature (S in R/S) comes from Greek for rotation to the left (levo-rotation; counterclockwise) – COO– H3N C H + H3N R *counter clockwise rotation = S = L Fisher projections define a chiral carbon with carbons in chain up and down and substituents left and right. For amino acids, the higher MW substituent (amino group) is on the left, its “L”. *arrangement of bonds Definition: Proteins are a linear polymers of L-a-amino acids. (generally composed of 20 different types) “L” refers to the old-style of configuration* nomenclature (S in R/S) comes from Greek for rotation to the left (levo-rotation; counterclockwise) ② ③ (S) ① Proteins The 4 S’s for Proteins: Size Shape Solubility Stability (R) ① ② ③ Size of Proteins The Size’s for Proteins are variable due to the length of the polymers: Protein polymers range from ~30-50 AA (insulin) to 50,000 AA (dystrophin) Smaller than ~30 AA are usually called peptides Protein diameters are much larger than Water: 10-20 Å in diameter to 1000 Å Size of Proteins Shape of Proteins The Shape’s for Proteins are variable due to the size of the polymer as well, but much more due to the AA composition and sequence of the amino acids in the polymer. HUGE variability!! All these variable shapes are governed by those non-covalent bonds we just discussed: H-bonds, hydrophobic effect, van der Waals, and ionic interactions. Shapes of Proteins: all same scale Shape of Proteins The STRUCTURE of proteins has been divided into four categories: 1) primary structure – sequence of amino acids acids 2) secondary structure – small units of repetitive structure repetitive structure 3) tertiary structure – overall 3D shape 4) quaternary structure –– shape shape of of ≥2 ≥2 chains chains Levels of Protein Structure primary structure – tertiary structure – secondary structure – quaternary structure – Levels of Protein Structure primary structure – tertiary structure – secondary structure – quaternary structure – Solubility of Proteins The Solubility's for Proteins are variable due to the size of the polymer and the composition and sequence of the amino acids in the polymer, but generally they are polar and thus soluble in water. As we will see, the amino acids have “R” groups that differ by their solubility, hence also proteins. Some proteins are not soluble; e.g., a-keratin Stability of Proteins The Stability's for Proteins are variable as well and the reasons are not completely known. Measuring protein concentration: Lab Most proteins are not colored. If so, then the degree of color is proportional to the concentration (Beer’s Law). • React with chemicals to create something that is “colored” (colorimetric) • Must be a product that is not dependent on different amino acids; specific to it being a polymer 1) Copper ions in base will react with the amide nitrogen supplanting the hydrogen with the copper making a complex that is colored. 2) Coomassie Brilliant blue DYE changes color when bound to peptide bonds. • Take advantage of absorbance of amino acids in the ultraviolet region of the spectrum. Figure 5-4 Measuring protein concentration: Lab Most proteins are not colored. If so, then the degree of color is proportional to the concentration (Beer’s Law). • React with chemicals to create something that is “colored” (colorimetric) • Must be a product that is not dependent on different amino acids; specific to it being a polymer 1) Copper ions in base will react with the amide nitrogen supplanting the hydrogen with the copper making a complex that is colored. 2) Coomassie Brilliant blue DYE changes color when bound to peptide bonds. • Take advantage of absorbance of amino acids in the ultraviolet region of the spectrum. Types of Proteins Familiar Egg white (mostly ovalbumin and lysozyme) a-keratin (hair, nails, feathers) Casein (milk protein) Zein (corn protein) Myosin/actin (muscle proteins) Collagen (tendons, cartilage, extra-cellular matrix, gelatin) Schratin (insect exoskeleton) Types of Proteins Based on Structure • Fibrous (a-keratin, myosin, F-actin, tubulin, collagen) • Globular (hemoglobin, enzymes, antibodies) Types of Proteins Based on Function • Enzymes—catalytic proteins • Binding or Transport Proteins (carry substances within the organism or membrane bound to transport in and out.) a. b. c. d. e. f. Globins (hemoglobin (Hb), Mb; carry di oxygen) Cytochromes (Fe in a porphorin ring; carry electrons) albumins (serum; carry fatty acids) immunoglobulins (antibodies, defense) receptor proteins (receive and respond to molecular signals) Genetic regulatory proteins regulate when, how, and to what extent a gene is expressed (transcription/translation factors) • Storage proteins store amino acids (casein, zein). • Signal proteins; hormonal and regulatory proteins—control physiological processes Types of Proteins Based on Function (cont.) • Structural proteins provide physical stability and movement (collagen, keratin, histones). • Motor proteins: convert chemical into kinetic energy (kinesin, dyenin, flagellin, myosin) Shapes of Enzymes: all same scale kinesin Three Representations of Lysozyme Complete descriptions of tertiary structure have been worked out for many proteins. C Hemoglobin Aldolase Bovine Carboxypeptidase A Carboxypeptidase A PDBid 3CPA Configuration versus Conformation EXAMPLE: In biology, peptides can have an amazing versatility in function. One example are the endorphins–signal molecules produced by the brain that are mimicked by analgesic drugs such as codeine, morphine, and heroin. The smallest endorphin is called Met-enkephalin which is an active penta-peptide sequence of Tyr-Gly-Gly-Phe-Met. Somehow the SHAPE of these drugs and this peptide must be similar to bind to the same pain receptors Configuration versus Conformation Met-enkephalin is biosynthesized from a larger protein called proopiomelanocortin (~200 amino acids). Can this peptide have the same shape as morphine? Configuration versus Conformation Met-enkephalin is biosynthesized from a larger protein called proopiomelanocortin (POMC) (~200 amino acids). Can this peptide have the same shape as morphine? Configuration versus Conformation Met-enkephalin: Tyr-Gly-Gly-Phe-Met Morphine: Configuration versus Conformation CONFORMATION is the spatial arrangement of substituent groups that are free to assume different positions in space WITHOUT breaking any covalent bonds due to free rotations. CONFIGURATION is the spatial arrangement by which substituent groups or atoms are covalently linked in a molecule. Different configurations REQUIRE breaking covalent bonds.