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Chapter 8. Nucleotides and Nucleic Acids Part 1. Nucleotides and Nucleic Acids. Learning Goals. Biological function of nucleotides and nucleic acids Structures of common nucleotides Structure of double-stranded DNA Structures of ribonucleic acids How Proteins bind to DNA.
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Chapter8 Nucleotides and Nucleic Acids Part 1
Nucleotides and Nucleic Acids Learning Goals • Biological function of nucleotides and nucleic acids • Structures of common nucleotides • Structure of double-stranded DNA • Structures of ribonucleic acids • How Proteins bind to DNA
Functions ofNucleotides and Nucleic Acids • Nucleotide Functions: • Energy for metabolism (ATP, GTP, CTP, UTP) • Enzyme cofactors (NAD+, NADP+, FAD) • Signal transduction (cAMP, cGMP) • Nucleic Acid Functions: • Storage of genetic info (DNA) • Transmission of genetic info (mRNA) • Processing of genetic information (ribozymes) • Protein synthesis (tRNA and rRNA)
Nucleotides and Nucleosides • Nucleotide = • Nitrogeneous base • Pentose • Phosphate • Nucleoside = • Nitrogeneous base • Pentose • Nucleobase = • Nitrogeneous base
b-N-Glycosidic Bond • In nucleotides the pentose ring is attached to the nucleobase via N-glycosidic bond • The bond is formed to the anomeric carbon of the sugar in b-configuration • The bond is formed: • to position N1 in pyrimidines • to position N9 in purines • This bond is quite stable toward hydrolysis, especially in pyrimidines • Bond cleavage is catalyzed by acid
Watson and Crick Had Three Sets of Data • Rosalind Franklin’s X-ray crystallography • Chargaff’s Rules • Chemical Structures of Nucleotides
Some of Chargaff’s Rules • DNA base composition varies between species. • DNA from different tissues of same species has the same base composition. • Base composition of a species does not vary with age, nutritional state, or change in environment. • No matter what species A = T and G = C and [purines] = [pyrimidines] which is A+G = T+C • Erwin Chargaff in the 1940’s worked out methods to measure each nucleotide in DNA. The rules made sense when applied to the Watson-Crick DNA structure.
DNA Bases – Pairing Suppose you isolated DNA from two unidentified species of bacteria: species X and species Y. You know that adenine makes up 32% of species X DNA and 13% of species Y DNA. How much of each nucleotide are present in these two DNAs? One species was isolated from a hot thermal spring, which is the most likely one?
The Beauty of the Watson-Crick Structure was that it gave a way to do Hi-fidelity Replication
Forces that hold two ssDNA dsDNA • H-bonds and 2. hydrophobic stacking • About equal in strength..look at the diagrams, where’s the water?
DNA Helix Forms A B Z
Lehninger 5th Edition is 1,263 printed pages + a few blanks pages are 21.5 cm wide x 27.5 cm high. Placing the pages next to each other then the book is How Long? Answers = 271.5 meters side by side .. or 347.3 meters tops to bottoms or in Sports terms: About 2.7 to 3.5 and football fields long. NOW EOC Problem 3: How long is your DNA? The average human has about 0.5 g DNA. The B-helix weighs about 10-18 g/1000 nucleotide pairs. What more information do you need…to get the answer? Do it !! How Long is Your Book Laid Page by Page?
B-Z JunctionsHow to Go from Right Handed to Left Handed Ha, et al. 2005. Crystal structure of a junction between B-DNA and Z-DNA reveals two extruded bases. Nature. 437:1183-1186. Samsung Biomedical Research Institute, Seol, Korea and Massachusetts Institute of Technology, Cambridge, MA.
B-Z Junction – Side View Z DNA is a higher energy form of the double helix…stabilized by negative supercoiling (generated by transcription or unwrapping from nucleosomes). Z DNA near the promoter stimulates transcription. Stabilized by proteins…Kd in nM range. But…can relax back to the B helix. Extruded bases may be site for DNA modification.
DNA Binding Proteins – It’s all in the Grooves EOC Problem 1 looks at H-bonding from the sides of the DNA strand..through the grooves.
Minor Groove is Also Important Minor Groove narrowing with AT tracts variation in shape. Enhances Arg Binding Rhos et al. Nature 461:1248 2009
Things to Know and Do Before Class Structure and chemistry of the nucleotides. Essence of Chargaff’s Rules. Structure and properties of the dsDNA and dsRNA helices. 4. BZ junctions. 5. How proteins bind to DNA. 6. EOC Problems: 1-3