Bi1_2009_Lecture4_full

Bi1_2009_Lecture4_full - You can use the electron density...

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Unformatted text preview: You can use the electron density equation to calculate an electron density map once you have amplitudes and phases for every hkl (h,k,l are indices for diffraction maxima in reciprocal space) Coordinates are deposited in the Protein Data Base (PDB) PyMol Molecular Viewer Will be used for PS2 and other sets throughout the course Tutorial on Bi1 website Demo by Toni Lee on Friday, April 10 4-6pm Here: (119 Kerckhoff) Macromolecular structure Love hides in molecular structures. Jim Morrison, Love Hides, from Absolutely Live, The Doors Macromolecules are created by covalently linking small molecules (monomers or subunits) into long chains or polymers. Sugars are energy sources for cells. Proteins catalyze reactions and perform MANY other functions in cells. Nucleic acids (DNA, RNA) store and transmit hereditary information. Little Alberts, Figure 2-27 Nucleic acid structure DNA ----------> RNA --------------> Protein Transcription Translation The information for the amino acid sequence of each protein is stored in DNA as a code. DNA is transcribed into RNA, which serves as a “messenger” that is translated into protein. Clicker question What is the significance of the structure of DNA? 1) 2) 3) 4) It explains how genetic material is copied. It explains how proteins are translated. It explains how mutations occur. It can be made into beautiful works of art. Clicker question Which part of the DNA structure explains how DNA is replicated? 1) 2) 3) 4) The sugar-phosphate backbone The deoxynucleotides The amino acids The basepairs Clicker question Which part of the DNA structure explains how DNA is replicated? A) B) C) D) The sugar-phosphate backbone The deoxynucleotides The amino acids The basepairs “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.” (J. Watson & F. Crick, 1953, Nature 171: 737-738) DNA is made from four nucleotide building blocks: Adenine (A), Thymine (T), Cytosine (C), Guanine (G) Little Alberts, Figure 2-25 DNA structure video Watson and Crick deduced the structure of DNA from this diffraction image What is the significance of the “X”? Find out at this website: http://www.pbs.org/wgbh/nova/photo51/ Find out more about Rosalind Franklin, the scientist who recorded this diffraction pattern, in this article: "Rosalind Franklin and the Double Helix," by Lynne Osman Elkin, Physics Today, March 2003 http://www.physicstoday.org/vol-56/iss-3/ p42.html The structure of DNA explains how genetic information is copied • • Each strand of the DNA double helix is complementary to its partner strand, so each can act as a template for synthesis of a new complementary strand (“semi-conservative” replication). Base-pairing allows a simple way for cells to pass on their genes to descendents. Incorrect DNA model Even Linus Pauling, a brilliant chemist who discovered -helices and -sheets in proteins, wasn’t infallible. But (important point here) he was thinking and proposing solutions to important problems. Triplet code The Genetic Code-- it’s (pretty much) universal 64 triplets encode 20 amino acids (most amino acids are encoded by more than one triplet) plus a termination signal (3 different stop codons). What about the structure of RNA? Single stranded RNA can fold into complicated 3D shapes resulting from intramolecular basepairing 07_05_RNA.jpg Hairpin structures result from regions of sequence that are complementary to each other (inverted repeats). Structure of a ribozyme, an RNA enzyme What do proteins do? • Catalysis -- enhancement of reaction rates (e.g., a polymerase makes polymers from monomers) • Transport and storage (e.g., hemoglobin) • Immune protection (e.g., antibodies) • Control of gene expression (e.g., repressors) • Mechanical support (e.g., collagen in skin and bone) What is an enzyme? • Enzymes are proteins* that catalyze (accelerate) chemical reactions. Many of their names end in “ase” (e.g., polymerase, kinase, protease). • Substrate: molecule at the beginning of the reaction. Product: molecule at the end of the reaction. • The activity of an enzyme is determined by its 3-D structure. • Enzymes lower the activation energy for a reaction. *Some RNA molecules can act as enzymes to catalyze reactions, but most enzymes are proteins. Proteins we will discuss in Bi 1 • DNA-binding proteins • Enzymes, including DNA and RNA polymerase, ribosomes* • HIV proteins • Antibodies and immune system proteins • Cytoskeletal proteins (actin, tubulin) Almost every time we discuss a function that is carried out in a cell or a virus, it is done by a PROTEIN*. Ribosomes contain proteins, but their catalytic activies are carried out by RNA Proteins are made from amino acids linked together by planar peptide bonds Clicker question: Peptide bonds are planar because the N-C’ bond has partial double bond character. Linus Pauling (Caltech) provided evidence for this when he was able to show that… 1) A trans conformation is favored for the N-C’ dihedral angle for most amino acids. 2) The distance measured for a peptide bond was shorter than expected for a typical C-N single bond. 3) N-C’ bonds break spontaneously in aqueous solvents. 4) Hemoglobin contains many double bonds. Clicker question: Peptide bonds are planar because the N-C’ bond has partial double bond character. Linus Pauling (Caltech) provided evidence for this when he was able to show that… 1) A trans conformation is favored for the N-C’ dihedral angle for most amino acids. 2) The distance measured for a peptide bond was shorter than expected for a typical C-N single bond. 3) N-C’ bonds break spontaneously in aqueous solvents. 1.45Å 1.33Å C N C Properties of the 20 amino acids in proteins See also http://www.imb-jena.de/IMAGE_AA.html and p. 74-75 of Essential Cell Biology Proteins are held together by noncovalent interactions Figure 3-9 Clicker question: the type of interaction most likely to occur between a glutamic acid residue and an arginine residue is… 1) Electrostatic 2) H-bond 3) VdW 4) Hydrophobic Glu Arg Clicker question: the type of interaction most likely to occur between a glutamic acid residue and an arginine residue is… 1) Electrostatic 2) H-bond 3) VdW 4) Hydrophobic Glu Arg PROTEIN STRUCTURE Primary structure: sequence (G S H S M R Y F Y T S . . .) Secondary structure: -helix, -sheet Tertiary structure: How the secondary structural elements are arranged to form a compact structure. -helix -helix Antiparallel -sheets Parallel -sheet Color conventions for amino acids www.cryst.bbk.ac.uk/PPS95/ course/3_geometry/peptide1.html See pages B8-B9 at end of your textbook Different ways to depict a protein structure Wire diagram Ribbon diagram Ball & stick of featured area Blue: positive Red: negative Space filling: van der Waals Surface representation (GRASP image) Petsko G.A., Ringe, D., Protein Structure and Function 2004, figure 5-5, pg. 173. Primary Structure: Amino Acid Sequence • Enter Somethign ...
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This note was uploaded on 09/25/2010 for the course BIO 1 taught by Professor Bakorman during the Spring '09 term at Caltech.

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