The Central Dogma of Molecular Biology
Defines the relationships between DNA, RNA, and protein in the transmission of genetic information into functional units of biological activity.
DNA RNA Protein
AJI SUTRISNO FOOD SCIENCE AND TECHNOLOGY UNIVERSITAS BRAWIJAYA (UB)
Nucleotides and nucleic acids
Nucleotides are the building blocks of nucleic acids
Nucleotide
RNA
DNA
Nucleotides also play other important roles in the cell
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) Structural components of many enzyme cofactors (NAD: nicotinamide adenine dinucleotide)
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 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
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Structure of nucleotides
Nucleotides have three characteristic components:
A phosphate group
A nitrogenous base
(pyrimidines or purine)
A pentose sugar
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Fig. 8-1
Phosphate Group
DNA Nucleotide
5
O O=P-O O
CH2 O N
C4
Sugar (deoxyribose)
C1 C3 C2
Nitrogenous base (A, G, C, or T)
Structure of nucleosides
Remove the phosphate group, and you have a nucleoside.
ATP is a nucleotide - energy currency
triphosphate
Base (adenine) Ribose sugar
DG = -50 kJ/mol
NAD is an important enzyme cofactor
nicotinamide
NADH is a hydride transfer agent, or a reducing agent. Derived from Niacin
Nucleotides play roles in regulation
Fig. 6-30
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.
The ribose sugar
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Ribose
Ribose (b-D-furanose) is a pentose sugar (5membered ring). Note numbering of the carbons. In a nucleotide, "prime" is used (to differentiate from base numbering).
5 4 3 2 1
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Fig. 8-3
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). The sugar prefers different puckers in DNA (C-2' endo) and RNA C-3' endo).
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Fig. 8-3
TWO TYPES OF SUGAR IN NUCLEIC ACIDS
Both retain a 3 hydroxyl group
The purine or pyrimidine base
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Pyrimidine and purine
Nucleotide bases in nucleic acids are pyrimidines or purines.
Know these!
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Fig. 8-1
Pyrimidine and purine
Nucleotide bases in nucleic acids are pyrimidines or purines.
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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
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Fig. 8-2
The phosphate
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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.
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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. 8-4
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Deoxyribonucleotides are abbreviated (for example) A, or dA (deoxyA), or dAMP (deoxyadenosine monophosphate)
The major deoxyribonucleotides
Fig. 8-4
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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)
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Fig. 8-4
The major ribonucleotides
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Fig. 8-4
Nucleotide nomenclature
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Nucleotide nomenclature
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Fig. 8-39
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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, and the 3' end lacks a nucleotide at the 3' end position.
Fig. 8-7
10/10/05
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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' Note that the backbone is polyanionic. Phosphate groups pKa ~ 0.
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Berg Fig. 1.1
10/10/05
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.
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Interstrand H-bonding between DNA bases
Watson-Crick base pairing
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Fig. 8-11
DNA structure determination
Franklin collected x-ray diffraction data (early 1950s) that indicated 2 periodicities for DNA: 3.4 and 34 . Watson and Crick proposed a 3D model accounting for the data.
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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, or 36 , per turn of the helix. Alternating deoxyribose and phosphate groups on the backbone form the outside of the helix. The planar purine and pyrimidine bases of both strands are stacked inside the helix.
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Fig. 8-15
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DNA structure
The furanose ring usually is puckered in a C-2' endo conformation in DNA. The offset of the relationship of the base pairs to the strands gives a major and a minor groove. In B-form DNA (most common) the depths of the major and minor grooves are similar to each other.
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Fig. 8-15
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Base stacking in DNA
C-G (red) and A-T (blue) base pairs are isosteric (same shape and size), allowing stacking along a helical axis for any sequence.
Base pairs stack inside the helix.
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Berg Fig. 1.4; 5.13
10/10/05
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
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Fig. 8-16
Nucleic acids
B form - The most common conformation for DNA. A form - common for RNA because of different sugar pucker. Deeper minor groove, shallow major groove A form is favored in conditions of low water. Z form - narrow, deep minor groove. Major groove hardly existent. Can form for some DNA sequences; requires alternating syn and anti base configurations.
36 base pairs Backbone - blue; Bases- gray
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Fig. 8-19
Nucleic acids
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Fig. 8-19
10/10/05
RNA has a rich and varied structure
WatsonCrick 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.
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Fig. 8-26
RNA displays interesting tertiary structure
Singlestranded RNA righthanded helix Yeast tRNAPhe (1TRA)
Hammerhead ribozyme (1MME)
T. thermophila intron,
A ribozyme (RNA enzyme) (1GRZ)
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Fig. 8-25
Fig. 8-28
The mother of all biomolecules (proteins at least)
Large subunit of the ribosome 1ffk
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