University:
Boston University
Course:
CAS BI 525 | Biology of Neurodegenerative Diseases
Academic year:

2023
Views:

318

Pages:

18
Author:

eishuma5iuk

Nucleic Acids A. Nucleotides 1. 2. 3. 4. parts nomenclature numbering properties B. Nucleic Acids 1. Polymer-bond 2. H-bonds 3. Roles a. Nucleotides b. Nucleic acids C. The 4 S’s 1. Size a. genomes b. RNAs 2. Solubility 3.Shape 4.Stability Nucleotides & Nucleic Acids 1 Definition of Nucleotides The Nitrogenous Bases of Nucleotides are Derivatives of Purine & Pyrimidine H H H H H H H Linkage to sugar 2 Chemical Structures of Nucleotide Bases (U) Sugars of Nucleotides are Either Ribose & Deoxyribose 3 Chemical Structures of Nucleotides Ester bond x3 Glycosidic bonds NTPs x3 H dNTPs 5’-Deoxyribonucleotide Chemical Structures of Nucleotides Ester bond x3 Glycosidic bonds NTPs x3 H dNTPs 5’-Deoxyribonucleotide 4 Nomenclature: Ribonucleotides You need to know structures, names, numbering, and symbols (both one-letter (A) and three-letter (AMP) codes). Nomenclature: Deoxyribonucleotides You need to know structures, names, numbering, and symbols (both two-letter (dA) and four-letter (dAMP) codes). 5 Nucleotides: Nomenclature -ine -osine -ylate -idine -idylate Aden Guan Cyt Cytos Thym Ur Nucleic Acid Bases, Nucleosides, and Nucleotides Nucleotide Extinction Coefficient at pH 7.0 lmax (nm) (M-1cm-1) x103 AMP 15.4 260 GMP 11.7 248 CMP 7.5 280 dTMP 9.2 270 UMP 9.9 260 6 Definition of Nucleic Acids Nucleic acid – polymer of nucleotides – directionality 5’à3’ When you write a sequence: ATCG It is assumed that the 5’-end is on the left and the 3’-end is on the right, unless otherwise labeled. Phosphodiester bonds 5’-ATCG-3’ 3’-GCTA-5’ same molecule 7 Complementary Base Pairing in DNA Figure 13.7 DNA Is a Double Helix (Part 1) 40 8 H H N G N N H N O N H N R N H N O N H N N R H H N C N N H H N R O N R H H O N H H N O H O H N N PREDICTS CHARGAFF PURINE:PYRIMIDINE RATIOS N N N N A T and When an A must pair with T When a C must pair with G N N O N N O N N R R R DISTANCE R to R IDENTICAL = REGULAR DS DNAR A = ACCEPTOR D = DONOR N R = “rest of Backbone” N O D N H H N N N R N N A H H N N O N R R N A D D D R H H N N O H C N O H A H N N H N G N H O N A N H N R H H N D A A N R N O N R N H O H T N N N O R 17 filling model of DNA. 9 Watson-Crick Base Pairs Double-stranded Single-stranded Stem-loop M1 RNA component of the enzyme RNase P 10 Roles of Nucleotides The most well known is ATP: • Energy rich (high energy of hydrolysis, but kinetically stable) includes, GTP, CTP, UTP • Carrier molecule (key intermediates in metabolism) UDP-sugars, CDP-lipids, NADH, FAD • Secondary messengers (cAMP, cGMP) • Other cofactors for enzymes Other Functions of Nucleotides: Energy Source 11 Roles of Nucleic Acids •Information storage •Information retrieval •Information translation •Information processing •Information preservation Key experiments by Griffiths, Avery, and Hershey & Chase The 4 S’s Size Solubility Shape Stability 12 The 4 S’s Size Solubility Shape Stability Nucleic Acids: Size Genome Sizes 13 Nucleic Acids: Size Genome Sizes (from DNA sequence) TABLE 24-2 DNA, Gene, and Chromosome Content in Some Genomes Total DNA (bp) Number of chromosomesa Approximate number of genes Escherichia coli K12 (bacterium) 4,641,652 1 4,494b Saccharomyces cerevisiae (yeast) 12,157,105 16c 6,340b Caenorhabditis elegans (nematode) 90,269,800 12d 23,000 Arabidopsis thaliana (plant) 119,186,200 10 33,000 Drosophila melanogaster (fruit fly) 120,367,260 18 20,000 Oryza sativa (rice) 480,000,000 24 57,000 Mus musculus (mouse) 2,634,266,500 40 27,000 Homo sapiens (human) 3,070,128,600 46 20,000 Note: This information is constantly being refined. For the most current information, consult the websites for the individual genome projects. aThe diploid chromosomes number is given for all eukaryotes except yeast. b Includes known RNA-coding genes. cHaploid chromosomes number. Wild yeast strains generally have eight (octoploid) or more sets of these chromosomes. dNumber for females, with two X chromosomes. Males have an X but no Y, thus 11 chromosomes in all. Nucleic Acids: Size RNA Sizes 14 The 4 S’s Size Solubility Shape Stability Nucleic Acids: Solubility The polymer is a poly-anion The pKa of the phosphodiester is ~2.0 Consequences: 1) A counter ion: required for solubility and stability. usually Na+, K+, and/or Mg+2 in cell, also use of polyamines; spermine & spermidine. 2) Easily separated by electrophoresis: Every nucleotide has one (1) negative charge. so charge/mass ratio is constant. so can separate by size (similar in concept to SDS-PAGE). 15 Nucleic Acids: Solubility Nucleic acids can be separated by gel electrophoresis. Polymers can be placed in a well in a semisolid gel and an electric field is applied across the gel. Negatively charged Nucleic acids move towards positive end. For polymers of the same shape, smaller polymers travel faster than larger polymers. For polymers of the same size, more compact topolgies travel faster than less compact ones. The 4 S’s Size Solubility Shape Stability 16 Nucleic Acids: Shape ANTIPARALLEL dsDNA PARALLEL dsDNA Nucleic Acids: Shape ANTIPARALLEL dsDNA PARALLEL dsDNA 3’ 3’ 5’ 3’ 3’ 5’ 5’ 5’ 17 Therefore, 10 bp/turn Nucleic Acids: Shape 36° 20 Å 3.4 Å 3’ 5’ 10 9 8 7 6° 6 34 Å At, 10 bp/turn x 3.4Å/bp = Pitch of 34Å 5 4 3 2 1 3’ 5’ 18