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Chapter 19 Nucleic AcidsChapter 19 Nucleic Acids
•Nucleic acidsNucleic acids represent the fourth major represent the fourth major class of biomolecules (proteins, class of biomolecules (proteins, carbohydrates, fats)carbohydrates, fats)
Like other Macromolecules- contain multiple similar monomeric units covalently joined to produce large polymers
Ch 19 Nucleic AcidsCh 20 DNA ReplicationCh 21 Transcription and RNA ProcessingCh 22 Protein Synthesis
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Chapter 19 Nucleic AcidsChapter 19 Nucleic Acids
•Nucleic acidsNucleic acids represent the fourth major represent the fourth major class of biomolecules (proteins, class of biomolecules (proteins, carbohydrates, fats)carbohydrates, fats)
•GenomeGenome - the - the genetic informationgenetic information of an of an organismorganism
1889: Isolated acidic molecule from nuclei (nucleic acid)1889: Isolated acidic molecule from nuclei (nucleic acid)1944: DNA is the mol that carries genetic information1944: DNA is the mol that carries genetic information
Oswald AveryOswald Avery1953: Watson/Crick determine structure of DNA 1953: Watson/Crick determine structure of DNA
Like other Macromolecules- contain multiple similar monomeric units covalently joined to produce large polymers
1953: James Watson and Francis Crick determine structure of 1953: James Watson and Francis Crick determine structure of DNA DNA
Feb. 28Feb. 28thth 1953: Eagle pub in Cambridge 1953: Eagle pub in Cambridge
““we have found the secret of life” we have found the secret of life”
Information specifying protein Information specifying protein structurestructure
• InformationInformation flowflow::
• DNADNA RNA RNAPROTEINPROTEIN
•TranscriptionTranscription - copying of the DNA - copying of the DNA sequence information into RNA sequence information into RNA
•TranslationTranslation - Information in RNA - Information in RNA molecules is translated during molecules is translated during polypeptide chain synthesispolypeptide chain synthesis
Reverse transcriptaseReverse transcriptase(retro-viruses)(retro-viruses)
F. Crick 1958: F. Crick 1958: Central dogmaCentral dogma
•Nucleic acids are Nucleic acids are polynucleotidespolynucleotides
•Nucleotides have Nucleotides have threethree components: components:
(1)(1) A five-carbon sugarA five-carbon sugar(2)(2) A weakly basic nitrogen A weakly basic nitrogen
basebase(3)(3) PhosphatePhosphate
Nucleotides Are the Building Blocks of Nucleic AcidsNucleotides Are the Building Blocks of Nucleic Acids
Unsaturated (double bonds)Planar and absorb UV
Nucleotides have Nucleotides have threethree components: components:
five-carbon sugarfive-carbon sugar
weakly basic nitrogen baseweakly basic nitrogen base
PhosphatePhosphate
Nucleotides Are the Building Blocks of Nucleic AcidsNucleotides Are the Building Blocks of Nucleic Acids
What type of bond?
Nucleic acids are Nucleic acids are polynucleotidespolynucleotides
Nucleotides have Nucleotides have threethree components: components: A five-carbon sugarA five-carbon sugarA weakly basic nitrogen A weakly basic nitrogen basebasePhosphatePhosphate
Nucleotides Are the Building Blocks of Nucleic AcidsNucleotides Are the Building Blocks of Nucleic Acids
• RibonucleosidesRibonucleosides contain three contain three
hydroxyl groups hydroxyl groups
(2’, 3’ and 5’)(2’, 3’ and 5’)
• DeoxyribonucleosidesDeoxyribonucleosides can be can be phosphorylated at the phosphorylated at the
3’ and 5’ positions3’ and 5’ positions
NucleotidesNucleotides
A A nucleotidenucleotide is assumed to be is assumed to be 5’-phosphate5’-phosphate unless specified otherwise unless specified otherwise
AMP=pA ATP=pppA
phosphate esters of nucleophosphate esters of nucleosidessides
Potential sites of phosphate: Potential sites of phosphate:
Macromolecules
Nucleoside vrs Nucleotide
Tues Quiz:
Know the difference between nucleoside/nucleotide, purine/pyrimidine
Be able to identify and name the base structures (adenine etc)
Name the nucleoside (adenosine etc)
Nucleotides Nucleotides joined by 3’-5’ joined by 3’-5’ phosphodiestphosphodiester linkageser linkages
Structure of the Structure of the tetranucleotide tetranucleotide pdApdGpdTpdCpdApdGpdTpdC
Nucleotides Nucleotides joined by 3’-5’ joined by 3’-5’ phosphodiester phosphodiester linkageslinkages
Primary structurePrimary structureExtended conformationExtended conformationLong and thinLong and thinDirectionality 5’-3’Directionality 5’-3’
Backbone: phosphate andBackbone: phosphate and3’,4’ and 5’ carbon and 3’ oxygen3’,4’ and 5’ carbon and 3’ oxygen
Erwin Chargaff: Erwin Chargaff: Chargaff rules:Chargaff rules: A and T are present in equal amounts in DNA A and T are present in equal amounts in DNA
Ratio of purine/pyrimidine always 1:1Ratio of purine/pyrimidine always 1:1
DNA is double stranded and A pairs with T (and C with G)DNA is double stranded and A pairs with T (and C with G)
Same with G and CSame with G and CA=TA=T
DNA Is Double-StrandedDNA Is Double-Stranded
G=CG=C
Watson and Crick used all the data---- double helix DNA structureWatson and Crick used all the data---- double helix DNA structure
Two strands run in opposite Two strands run in opposite directionsdirections
Bases in opposite strands Bases in opposite strands pair by pair by complementarycomplementary hydrogenhydrogen bondingbonding
Adenine (A) - Thymine (T)Adenine (A) - Thymine (T)
Guanine (G) - Cytosine (C) Guanine (G) - Cytosine (C)
Two Antiparallel Strands Two Antiparallel Strands Form a Double HelixForm a Double Helix
Complementary:Complementary: can serve as templateFor other strand
Equal distance between backbone
(Purine/pyrimidine 1:1)
• ComplementComplementary base ary base pairing and pairing and stacking in stacking in DNADNA
Stacking of basesStacking of basesStabilizes dsDNAStabilizes dsDNA
Cooperative Cooperative non-covalent non-covalent Within hydrophobicWithin hydrophobicinteriorinterior
Helix allowseffective stacking
Three dimensional structure of Three dimensional structure of DNADNA
• A double helix has two grooves A double helix has two grooves of unequal width: of unequal width: major groovemajor groove and and minor grooveminor groove
• Within each groove base pairs Within each groove base pairs are exposed and are accessible are exposed and are accessible to interactions with other to interactions with other moleculesmolecules
• DNA-binding proteins can use DNA-binding proteins can use these interactions to “read” a these interactions to “read” a specific sequencespecific sequence
B-DNAB-DNA is a is a rightright--handedhanded helixhelix, diam. = 2.37nm, diam. = 2.37nm
• Rise (distance between stacked bases) Rise (distance between stacked bases) =0.33nm=0.33nm
• Pitch (distance to complete one turn) = 3.40 Pitch (distance to complete one turn) = 3.40 nmnm
• 10.4 base pairs per turn10.4 base pairs per turn
Structure of helix allows access to info
Two alternative structures to B-DNA:Two alternative structures to B-DNA:A-DNA A-DNA (forms when DNA is dehydrated)(forms when DNA is dehydrated)Z-DNAZ-DNA (when certain sequences are present) (when certain sequences are present)
A-DNA is more tightly wound than B-DNA, and has grooves of A-DNA is more tightly wound than B-DNA, and has grooves of similar widthsimilar width
Z-DNA has no grooves and a left-handed helixZ-DNA has no grooves and a left-handed helix
Both A-DNA and Z-DNA exist Both A-DNA and Z-DNA exist in vivoin vivo in short regions of DNA in short regions of DNA
AA BB ZZ
Conformations of Double-Stranded DNAConformations of Double-Stranded DNA
G/C rich regions dG residue: base is in Syn conformationG/C rich regions dG residue: base is in Syn conformation
Race to determine the structure of Race to determine the structure of DNA DNA
Watson and Crick model
1953
DATA:
Chargaff rules ; A=T and G=C
Card board cut out puzzle
Proper tautomeric forms of bases
What data did they collect on their own ?????
1944 realized DNA carried genetic info
1947 Crick knew no biology, little organic chemistry or crystallography1951 met Watson1953 determined structure of DNA1954 finished PhD on X-ray diffraction of proteins1962 Nobel prize
Evidence for helical nature
Race to determine the structure of Race to determine the structure of DNA DNA
“Photo 51” Rosalind Franklin
Watson and Crick model
1953
1953
Linus Pauling----wrong !!
1953 paper incorrect triple helical model
1951 same triple helical model thrown out by W/C
Rosalind tore it apart…it ignored her data
1951 solved alpha helix
Diff sizes of bases—had to be on outside Did not have good x ray data—Wilkins turned him down
How to pack neg charge in center? 10x more water in molecule than the model would allow
Did not visit Franklin
Two-fold symmetry (not triple)Cross-like reflections of helix