Ch6-120208 - CHEM 350: Introduction to Biological Chemistry...

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Unformatted text preview: CHEM 350: Introduction to Biological Chemistry Brian Lee, Ph.D. [email protected] Office: Neckers 146G or 324 Phone: 453-7186 Hours: 9:30am to 10:30am or by appointment Website: https:/ / Textbook (required, U.S. edition only) Fundamentals of Biochemistry, 3rd Ed., Voet, Voet & Pratt. Study Guide (recommended) Student Companion to Fundamentals of Biochemistry, 3rd Ed. Help Desk Tuesday 6:30 to 7:30 pm in Neckers 218 Thursday 5:00 to 6:00 pm in Neckers 410 Announcements Undergraduate Research Opportunities Research for credit (such as CHEM 396 or CHEM 496) Student worker ($8.00 per hour) ( Undergraduate Assistantships ( McNair Scholars Program ( REACH Awards Competition ( Summer Research Experiences for Undergraduates (REU) For other REU programs, search the National Science Foundation site: Students must contact the individual sites for information and application materials. NSF does not have application materials and does not select student participants. A contact person and contact information is listed for each site. Assignments Read Chapter 6 Proteins: 3D Structure Chapter 6 Problems Second Midterm Exam, Wednesday February 29th Chapters 6 through 9 All exams are cumulative Help Desk Tuesday 6:30 to 7:30 pm in Neckers 218 Thursday 5:00 to 6:00 pm in Neckers 410 Tertiary Structure Ferritin - all alpha helical protein Tertiary structure: three-dimensional structure of a single polypeptide chain. Fibrous proteins: polypeptide chains arranged in elongated repeated structures (typically contain a single type of secondary structure: alpha helix or beta strand). collagen Globular proteins: folded into compact globular shape (typically several types of secondary structure). carboxypeptidase A -keratin (skin, hair, nails) Fibrous Protein: Intermediate Filament Proteins -keratin: right handed -helices oriented parallel to each other forming a left-handed super-twisted coiled coil (technically this is quartenary structure) Coiled coil structure of -keratin due to 7 residue pseudorepeat: a-b-c-d-e-f-g a and d – nonpolar hydrophobic Figure 6-15b Cross-linking between polypeptide chains increases strength of -keratin in hair, claws, horns, hooves and skin. Collagen (connective tissue, bone matrix, cornea) left handed right handed Left handed polypeptide helices twisted around each other in a right handed superhelical structure Rope-like structure is stabilized by hydrogen bonds between chains glycine Collagen Triple Helix (X-ray structure by Helen Berman) Glycine close packing and inter-chain hydrogen bonding. Collagen triple helix Tripeptide repeat, Gly-X-Y X = Pro Y = 4-Hyp (4-hydroxyproline) Interchain hydrogen bonds Covalent cross-links between lysine and histidine residues. Collagen triple helices are further cross-linked through allysine, 5-hydroxylysine, and histidine (at X or Y positions) Lysyl oxidase is the only enzyme implicated in the process of creating cross-links. The copper containing enzyme catalyzes the conversion of lysine to allysine (aldehyde), which is highly reactive. -aminopropionitrile from sweet pea (Lathyrus odoratus) inhibits lysyl oxidase and causes osteolathyrism. Weak connective tissue and paralysis. Hydroxylation - stabilizes collagen protein in connective tissue (ligaments) catalyzed by prolyl 4-hydroxylase. Prolyl 4-hydroxylase, a heme protein, requires vitamin C and deficiency causes degeneration of connective tissue (scurvy) Electron micrograph of collagen fibrils shows a banded appearance due to gaps in the overlapping packing of helices. Cross-section of layered beta sheets Silk fibroin from spider spinnerets Silk fibroin (spiders and insects): beta-conformation. Ala and Gly allowing close packing between beta sheets Globular Proteins Myoglobin - the first protein structure, determined by X-ray crystallography 1959 by Max Perutz and John Kendrew Xray crystallography Proteins crystals show a diffraction pattern which is dependent on the electron density of protein atoms. At high resolution the electron density map shows the position of individual atoms. Amino acid residues and the peptide backbone can be fitted into the electron density map of a protein. NMR Spectroscopy Distances between hydrogen nuclei can be measured directly due to the nuclear Overhauser effect (NOE) for distances less than 5 Ångstroms. A list of measured distances is used to calculate the structure of a protein. interior side exterior side Polar versus non-polar residues in protein structures -helix -sheet Polar residues Non-Polar residues Cytochrome c The non-polar residues occupy the interior and polar surface residues interact with solvent Myoglobin heme Leu, Ile, Val, Phe Heme (a prosthetic group) allows myoglobin to bind oxygen. Stable arrangements of several elements of secondary structure and the connections between them are known as super-secondary structures or secondary structure motifs. Motifs are various combinations of secondary structure motif – parallel beta sheet - hairpin – two or more anti-parallel beta strands motif – helices pack at an optimal angle -Greek key motif – anti-parallel beta strands with Greek pottery pattern topology Figure 6-28 Smaller motifs can be seen in larger structural motfis. Classification of Protein Folds protein family - structural similarity due to strong evolutionary relationship superfamily - structural and functional similarity, but no clear evolutionary relationship All / All + Classification by Topology – connections between secondary structure elements. cytochrome b562 4 helix bundle immunoglobulin beta sandwich lactate dehydrogenase 6 strand parallel sheet Multi-domain structures -single poly-peptide chain -folded sub-domains -usually flexible linkers Glyceraldehyde 3-phosphate dehydrogense Enzyme active site is between domains. N-terminal domain contains dinucleotide binding domain (NAD+) Conservation of structure through evolution Heme binding site in cytochrome c Quarternary Structure and Symmetry Multimers (or Oligomers) Hemeglobin - 4 separate peptide chains 2 alpha subunits (protomer) 2 beta subunits (protomer) Multimeric proteins can have rotational symmetry or helical symmetry. Rotational symmetry - subunit superposition after rotation about one or more axis of symmetry. Cyclic symmetry (Cn) - rotation about a single axis Dihedral symmetry (Dn) - Multiple axis of symmetry A twofold axis intersects an n-fold axis at right angles Higher order symmetry is often seem in virus particles. Icosahedral symmetry is the most common. 3 non-perpendicular axes of symmetry Figure 6-34 What holds a protein together (section 4)? How do proteins fold into the correct structure (section 5)? Protein Stability -Hydrophobic effect -Electrostatic interactions -Disulfide bonds -Metal ion coordination -Flexibility Hydrophobic interactions stabilize protein structure and drive protein folding through exclusion of water Figure 6-35 Salt bridges Figure 6-36 Disulfide bonds in Ribonuclease A Metal ion coordination Zinc finger motif -zinc ion -cysteine and histidine Other metals: Iron-sulfur clusters Copper Magnesium Calcium Protein flexibility -increases entropy -active site access -induced fit binding -enzyme kinetics -membrane transport ...
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This note was uploaded on 03/26/2012 for the course CHEM 350 taught by Professor Lee during the Spring '08 term at SIU Carbondale.

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