Lecture3_9_9_08 - Lecture 3 Chapter 2 Stryer • amino acids-structure-stereochemistry-acid/base properties • peptides-structure-biological

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Unformatted text preview: Lecture 3 Chapter 2: Stryer • amino acids -structure -stereochemistry -acid/base properties • peptides -structure -biological activities • proteins -structure human insulin: a protein hormone crucial for maintaining appropriate blood sugar level Proteins • Proteins are linear polymers built of monomer units called amino acids. They fold into three-dimensional structures that are important for their functions. • Proteins contain a wide range of functional groups. These groups are chemically reactive and can participate in numerous types of interactions. • Proteins can interact with one another and other biological molecules to form complex assemblies. • Some proteins are rigid, whereas others display a considerable degree of flexibility. This degree of flexibility is often related to their biological roles. The protein lactoferrin: undergoes a substantial conformational change upon metal (Fe) binding. A protein component of the DNA replication machinery: the two clamps (subunits) surround the DNA. amino acid structure "! carbon" * S configuration "side chain" known as an !-amino acid, due to the location of the amino group on the ! carbon (! to the carbonyl) The standard (DNA-encoded) amino acids found in proteins possess the L stereochemistry. D-amino acids are produced in certain organisms, but are not found in their proteins. amino acids are charged (ionized) under cellular conditions (pH ~ 7.0) Proline - side chain is joined to the !carbon atom and amino group Aliphatic side chains Aromatic side chains Aliphatic hydroxyl side chains Amide side chains Sulfhydryl, or thiol, side chains basic side chains acidic side chains know pKa values Histidine ionization titrating an amino acid: glycine although the exact protonation state of the molecule depends on the pH of the solution, at no point is it uncharged Gly is a simple case-amino acids with ionizable side chains would exhibit a more complex titration curve, depending on the exact pKa of the side-chain group Titration curve for an amino acid with three ionizable groups Titration curve for an amino acid with three ionizable groups Know these (and structures)! Why does nature use serine and not homoserine in proteins? amino acids link to form polypeptides: primary protein structure peptides • short polymers of amino acids • each amino acid unit is called a residue • nomenclature based on number of residues 2 = dipeptide; 3 = tripeptide • 'many' residues in a single chain = polypeptide Peptide-bond formation: is this a spontaneous reaction? • with the modular nature of a peptide, and availability of 20 amino acids, the number of peptides is immense (20n) • if the peptide chain exhibits a specific conformation in solution, that is known as secondary structure • inverting the sequence (primary structure) of a peptide yields a completely different molecule, i. e. Gly-Ala-Val ! Val-Ala-Gly side chain ionization If the solution pH < pKa of the functional group, the group is protonated If the solution pH > pKa of the functional group, the group is unprotonated planarity & rigidity due to resonance in the peptide (amide) bond Cross-links: the formation of a disulfide bond from two cysteine residues is an oxidation reaction C!-C N-C! C-N (amide) three types of bonds in a peptide backbone (repeated); C-N is rigid, other two are flexible (rotation about bonds) Typical bond lengths favored X-pro bonds Rotation about bonds of a polypeptide Ramachandran diagram Values of " and # Secondary structures of polypeptides ! helix ! helix Pay close attention to the hydrogen-bonding patterns in the ! helix. Every backbone amide is engaged in H bonding as both a donor (C=O) and acceptor (N-H) except at the N terminus and C terminus. The internal H bonds are between the i and i+3 residues, and all C=O point in the same direction (see previous slide). Notice: the amino-acid side chains are projected towards the outside of the helix. Secondary structure: the ! helix Other factors that stabilize the ! helix (besides H bonding): Electrostatic bonding interactions between adjacent residues, or residues that are 3-4 residues apart. Asp100 Large R groups or repulsive electrostatic charges between adjacent residues can be destabilizing. ! helices do not like to have Pro or Gly residues: they are destabilizing. essentially all ! helices in proteins are righthanded Arg103 representations of the ! helix Another common secondary structure element in proteins: the " strand Ferritin, an iron-storage protein, is built from a bundle of ! helices Antiparallel " sheet Parallel " sheet H bonds between adjacent " strands are 'parallel' R groups alternate between projecting above and below adjacent " strands run in opposite directions H bonds between adjacent " strands are 'angled' R groups alternate between projecting above and below adjacent " strands run in the same direction Mixed " sheet note: peptide backbone is extended representations of the " sheets Fatty acidbinding protein, a protein rich in " sheets Secondary structure: the " turn allows the peptide chain to reverse direction Secondary structure: proline and the cis amide conformation Pro is unique: it can adopt the cis conformation; this form introduces more of a 'turn' that fits well into " turns. Ramachandran plots Secondary structure: not all amino acids are equally likely to be found in a given type of 2° structure notice: Pro and Gly have opposing tendencies Secondary structure: recap Secondary (2°) structure is the arrangement of amino-acid residues in a segment of polypeptide chain in which each residue has a specific special relationship with its neighbors. The most common types of 2° structure are ! helix, " sheet, and " turn. The common 2° structures have well-defined torsion angles. Hydrogen bonding is an important stabilizing factor in protein 2° structures. !-helical coiled coil Fibrous proteins provide structural support for cells and tissues ...
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This note was uploaded on 08/04/2010 for the course CHM 6620 taught by Professor Dr.christinechow during the Fall '08 term at Wayne State University.

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