Structure and Function of Nucleic Acids

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1 Structure and Function of Nucleic Acids E T Nyahangare

2 Class Assignment 1. Write notes and outline the role of the following in protein biosynthesis a. DNA replication b. Transcription c. Genetic code 2. 2 planned tests - nucleic acids - bioenergetics

3 The nucleus contains the cell s DNA (genome) RNA is synthesized in the nucleus and exported to the cytoplasm Nucleus Cytoplasm replication DNA transcription RNA (mrna) translation Proteins

4 Nucleic Acids Long, thread-like polymers made up of a linear array of monomers (units) called nucleotides e.g DNA & RNA Historical perspective Friedrich Miescher in 1869 isolated what he called nuclein from the nuclei of pus cells Nuclein was shown to have acidic properties, hence it became called nucleic acid

5 Nucleotides and nucleic acids Nucleotides are the building blocks of nucleic acids Nucleotide RNA DNA 1 Nucleotides also play other important roles in the cell

6 Roles of nucleotides Building blocks of nucleic acids (RNA, DNA) Analogous to amino acid role in proteins Energy currency in cellular metabolism (ATP: adenosine triphosphate) Allosteric effectors Structural components of many enzyme cofactors (NAD: nicotinamide adenine dinucleotide) 2 As 102

7 Roles of nucleic acids DNA contains genes, the information needed to synthesize functional proteins and RNAs DNA contains segments that play a role in regulation of gene expression (promoters) Ribosomal RNAs (rrnas) are components of ribosomes, playing a role in protein synthesis 3

8 MRNA Messenger RNAs (mrnas) carry genetic information from a gene to the ribosome Transfer RNAs (trnas) translate information in mrna into an amino acid sequence RNAs have other functions, and can in some cases perform catalysis

9 Structure of nucleotides Nucleotides have three characteristic components: A phosphate group A nitrogenous base (pyrimidines or purine) A pentose sugar 4 Fig. 8-1

10 Structure of nucleosides Remove the phosphate group, and you have a nucleoside. H 5

11 ATP is a nucleotide - energy currency triphosphate Ribose sugar Base (adenine) DG = -50 kj/mol 6

12 NAD is an important enzyme cofactor nicotinamide NADH is a hydride transfer agent, or a reducing agent. Derived from Niacin 7 Fig

13 NUCLEOTIDE STRUCTURE PHOSPATE SUGAR Ribose or Deoxyribose BASE PURINES PYRIMIDINES Adenine (A) Guanine( G) Cytocine (C) Thymine (T) Uracil (U) NUCLEOTIDE

14 Structure of nucleotides Know this Below is the general structure of a nucleotide. The pentose sugar, the base, and the phosphate moieties all show variations among nucleotides. 9

15 The ribose sugar 10

16 Ribose Ribose (b-d-furanose) is a pentose sugar (5- membered ring). Note numbering of the carbons. In a nucleotide, "prime" is used (to differentiate from base numbering) Fig. 8-3

17 Ribose An important derivative of ribose is 2'-deoxyribose, or just deoxyribose, in which the 2' OH is replaced with H. Deoxyribose is in DNA (deoxyribonucleic acid) Ribose is in RNA (ribonucleic acid). 12 Fig. 8-3

18 Spot the difference RIBOSE DEOXYRIBOSE CH 2 OH O OH CH 2 OH O OH C C C C H H H H H H H H C C C C OH 2007 Paul Billiet ODWS OH OH H

19 The purine or pyrimidine base 13

20 Pyrimidine and purine Nucleotide bases in nucleic acids are pyrimidines or purines. 14 Fig. 8-1 Know these!

21 Major bases in nucleic acids Know these! The bases are abbreviated by their first letters (A, G, C, T, U). The purines (A, G) occur in both RNA and DNA Among the pyrimidines, C occurs in both RNA and DNA, but T occurs in DNA, and U occurs in RNA 16 Fig. 8-2

22 Some minor bases Fig. 8-5 Fig Methylcytidine occurs in DNA of animals and higher plants N 6 -methyladenosine occurs in bacterial DNA 17

23 The phosphate group 18

24 Variation in phosphate group camp Adenosine 3', 5'-cyclic monophosphate (cyclic AMP, or camp) is an important regulatory nucleotide. In hydrolysis of RNA by some enzymes, ribonucleoside 2',3'-cyclic monophosphates are isolable intermediates; ribonucleoside 3'- monophosphates are end products Another variation - multiple phosphates (like ATP). Fig. 8-6, x

25 Nucleotides in nucleic acids Bases attach to the C-1' of ribose or deoxyribose The pyrimidines attach to the pentose via the N-1 position of the pyrimidine ring The purines attach through the N-9 position Some minor bases may have different attachments. 20

26 Deoxyribonucleotides 2'-deoxyribose sugar with a base (here, a purine, adenine or guanine) attached to the C-1' position is a deoxyribonucleoside (here deoxyadenosine and deoxyguanosine). Phosphorylate the 5' position and you have a nucleotide(here, deoxyadenylate or deoxyguanylate) Fig Deoxyribonucleotides are abbreviated (for example) A, or da (deoxya), or damp (deoxyadenosine monophosphate)

27 The major deoxyribonucleotides Fig

28 Ribonucleotides The ribose sugar with a base (here, a pyrimidine, uracil or cytosine) attached to the ribose C-1' position is a ribonucleoside (here, uridine or cytidine). Phosphorylate the 5' position and you have a ribonucleotide (here, uridylate or cytidylate) Ribonucleotides are abbreviated (for example) U, or UMP (uridine monophosphate) 23 Fig. 8-4

29 The major ribonucleotides 24 Fig. 8-4

30 Nucleotide nomenclature 25

31 Nucleic acids Nucleotide monomers can be linked together via a phosphodiester linkage formed between the 3' -OH of a nucleotide and the phosphate of the next nucleotide. Two ends of the resulting polyor oligonucleotide are defined: The 5' end lacks a nucleotide at the 5' position, 27 Fig. 8-7 and the 3' end lacks a nucleotide at the 3' end position.

32 Sugar-phosphate backbone The polynucleotide or nucleic acid backbone thus consists of alternating phosphate and pentose residues. The bases are analogous to side chains of amino acids; they vary without changing the covalent backbone structure. Sequence is written from the 5' to 3' end: 5'-ATGCTAGC-3 28 Berg Fig. 1.1

33 Compare polynucleotides and polypeptides As in proteins, the sequence of side chains (bases in nucleic acids) plays an important role in function. Nucleic acid structure depends on the sequence of bases and on the type of ribose sugar (ribose, or 2'-deoxyribose). Hydrogen bonding interactions are especially important in nucleic acids. 31

34 Interstrand H-bonding between DNA bases Watson-Crick base pairing 32 Fig. 8-11

35 DNA structure determination Franklin collected x-ray diffraction data (early 1950s) that indicated 2 periodicities for DNA: 3.4 Å and 34 Å. Watson and Crick proposed a 3- D model accounting for the data. 33

36 DNA structure DNA consists of two helical chains wound around the same axis in a right-handed fashion aligned in an antiparallel fashion. There are 10.5 base pairs per turn of the helix. Alternating deoxyribose and phosphate groups on the backbone form the outside of the helix. The purine and pyrimidine bases of both strands are stacked inside the helix. 34 Fig. 8-15

37 DNA strands The antiparallel strands of DNA are not identical, but are complementary. This means that they are positioned to align complementary base pairs: C with G, and A with T. So you can predict the sequence of one strand given the sequence of its complement. Useful for information storage and transfer! Note sequence conventionally is given from the 5' to 3' end 37 Fig. 8-16

38 RNA has a rich and varied structure Watson- Crick base pairs (helical segments; Usually A-form). Helix is secondary structure. Note A-U pairs in RNA. DNA can form structures like this as well. 40 Fig. 8-26

39 RNA displays interesting tertiary structure Singlestranded RNA righthanded helix Yeast trna Phe (1TRA) Hammerhead ribozyme (1MME) T. thermophila intron, A ribozyme (RNA enzyme) (1GRZ) 41 Fig Fig. 8-28

40 The mother of all biomolecules (proteins at least) Large subunit of the ribosome 1ffk 42

41 Ribonucleic acid (RNA) 3 main types mrna, trna, r RNA Transfer RNA (trna) Forms 15% of all RNA Consists of 75 90% nucleotides which form a clover shape Just over 20 types each capable of carrying a specific a. a Amino acids transported from the cytoplasm to the ribosomes during protein synthesis It can be used more than once in Protein synthesis WHY?? Genetic code have multiple codons coding 4 one a. a

42 mrna Forms 3 5 % of all RNA Consists of single strand of nucleotides made in the nucleus from DNA by transcription (mirror image of I strand of the DNA) Transcription is catalysed by RNA polymerase many types and they form templates for protein synthesis Exist in the cell for a short time

43 rrna 80% of total RNA Consists of > 1000 nucletides which can be either a single strand or a helix (when the strand falls back on itself) Made in the nucleolus by DNA found in the ribosomes Factory site for protein synthesis (where mrna is translated into the primary structure of proteins)

44 Comparison of DNA & RNA DNA RNA Organic Bases A, G, T, C A, G, U, C Strands Double helix Single strand stability More stable less sugar deoxyribose ribose occurence permanent temporal Solubility Types Insoluble One Soluble 3 types Concentration Position Constant Mostly Nuclei Varies according to cell type Throughout cell