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9/14/05 BCOR 011

Nucleic Acids

Lecture 7Macromolecules #3

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Nucleic AcidsNucleic AcidsMonomer UnitsMonomer Units PolymersPolymers““Nucleotides”Nucleotides” ““PolynucleotidePolynucleotide

Chains”Chains”ribonucleotidesribonucleotidesATP GTP NADHATP GTP NADHCTPCTP UTP FADHUTP FADH22

ADP, AMP, ADP, AMP, cAMPcAMP, GDP, GDP

deoxydeoxyribonucleotidesribonucleotidesddATP ATP ddGTPGTPddCTP CTP (d)(d)TTPTTP

RNARNA

DNADNA

RRiboibo NNucleic ucleic AAcid cid

DDeoxyriboeoxyribo NNucleic ucleic AAcid cid

--Energy Carriers of the CellEnergy Carriers of the Cell--Building Blocks of RNABuilding Blocks of RNA

--Signaling and RegulatorySignaling and Regulatorymolecules of Processesmolecules of Processes

--Building Blocks of DNABuilding Blocks of DNAHugeHuge PolymerPolymer

Medium to Large PolymerMedium to Large Polymer--mmRNARNA--rrRNARNA--ttRNARNA

Information RepositoryInformation Repository“Hereditary Information”“Hereditary Information”

messenger RNAmessenger RNA

ribosomal RNAribosomal RNAtransfer RNAtransfer RNA

informationalinformationalStructuralStructuralcatalyticcatalytic

informationalinformationalstructuralstructural

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NucleotidesNucleotides3 components of monomer3 components of monomer

AdenineAdenineGuanineGuanineCytosineCytosine

UracilUracil/Thymine/Thymine

NitrogenousNitrogenousBaseBase PhosphatePhosphate

one or moreone or more

RiboseRiboseDeoxyDeoxyriboseribose

MonoMono--DiDi--TriTri--

SugarSugaraldoaldo Pentose Pentose

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Nitrogenousbase

Nucleoside

O

O

O−

−O P CH2

5’C

3’CPhosphategroup

Pentosesugar

(b) NucleotideFigure 5.26

O

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Nitrogenous BasesNitrogenous BasesFlatFlat Aromatic Aromatic NonNon--polarpolar

purinespurines33

22

1166

5577

44

88

99

pyrimidinespyrimidines11

33

22

44

55

66

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Polar Polar Edge: Edge: hydrogenhydrogen--bonding bonding edge edge Nitrogenous BasesNitrogenous Bases

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Assemble Nucleotides Assemble Nucleotides by by Condensation Dehydration Condensation Dehydration RxnsRxns..

nucleonucleosidesideuradineuradine

riboseribose uraciluracil 2’2’3’3’

1’1’4’4’

5’5’22

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445566

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Assemble Nucleotides Assemble Nucleotides by by Condensation Dehydration Condensation Dehydration RxnsRxns..

phosphatephosphate

nucleonucleotidetide

PhosphoPhospho--esterester

nucleosidenucleoside

Uridine Uridine monophosphatemonophosphate

(UMP)(UMP)

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PhosphoPhospho--anhydrideanhydride

ααββγ γ

ββ and and γγ are High energy bondsare High energy bonds

““carried” energy of ATP, GTP,CTP, UTPcarried” energy of ATP, GTP,CTP, UTP

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α α phosphatephosphate & & 3’ hydroxyl3’ hydroxylcan form can form didi--esterester

5’ to 3’ 5’ to 3’ phosphodiesterphosphodiesteris the basis of is the basis of

polynucelotide polynucelotide backbonebackbone 12

•• Nucleotide polymersNucleotide polymers– Are made up of nucleotides linked by

the ––OH group on the 3´ carbonOH group on the 3´ carbon of one nucleotide and the phosphate on the 5´phosphate on the 5´carbon on the next

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2’ OH2’ OH

2’ hydroxyl2’ hydroxylmakes RNAmakes RNAmore labilemore labile

in alkaline solutionsin alkaline solutions> pH 9> pH 9

2’2’deoxydeoxy

143’3’

5’5’ 3’3’

AntiparallelAntiparallelstrandsstrands

5’5’

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• The nitrogenous bases in DNA– Form hydrogen bonds in a complementary fashion (A with T only, and C with G only)

Why ?Why ?

Why not just HWhy not just H--bond with water ?bond with water ?165’5’

3’3’

3’3’

5’5’

BaseBasestackingstacking

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SugarSugar

SugarSugar

SugarSugar

5’5’POPO44

SugarSugar

POPO44

3’3’

POPO44

POPO445’5’

3’3’

polar

polar

polar

polar

polar

polarpolar

polar

hydrophobichydrophobic

hydrophobichydrophobic

hydrophobichydrophobic

hydrophobichydrophobic

Hydrophobic Interactions Hydrophobic Interactions –– driving force for double helixdriving force for double helix

Hydrogen bonding Hydrogen bonding –– stabilizes double helixstabilizes double helix 18

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ComplementaryComplementaryStrandsStrandsare theare the

Basis forBasis forfaithfulfaithful

copying copying ofofbase sequencebase sequencein the polymerin the polymer

The The sequencesequenceof basesof bases

ISISthe hereditarythe hereditaryinformationinformation

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Primary Structure:Primary Structure:Order of amino acids determined byOrder of amino acids determined by

a stretch of DNA sequencea stretch of DNA sequence

3 letter code3 letter code

64 possible64 possible“words”“words”

5’5’3’3’

gln serglu hisgln argthr stopala

TGA

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1

2

3

Synthesis ofmRNA in the nucleus

Movement of mRNA into cytoplasm

via nuclear pore

Synthesisof protein

NUCLEUS

CYTOPLASM

DNA

mRNA

Ribosome

AminoacidsPolypeptide

mRNA

Figure 5.2524

Summary:Summary:*Nucleotides and*Nucleotides and polynucleotidespolynucleotides*Numerous roles: *Numerous roles: informational,informational,

energy metabolismenergy metabolism, , signalingsignaling*Nucleotide composition: *Nucleotide composition:

nitrogenous basenitrogenous base, , pentose sugarpentose sugar, , & phosphates& phosphates

**RNARNA vs. vs. DNADNA: : structurallystructurally, , functionallyfunctionally

**PhosphodiesterPhosphodiester & & phosphoanhydridephosphoanhydride bondsbonds

**Double HelixDouble Helix:Base pairing & Base Stacking:Base pairing & Base Stacking

*Nucleic acid *Nucleic acid sequencesequence as informationas information

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Griffith: Griffith: something from bacteria transfers genetic traitsomething from bacteria transfers genetic trait

Avery, Avery, MacLeod and McCarty MacLeod and McCarty –– that somethingthat somethingis nucleic acid, not protein, carbohydrate or lipidis nucleic acid, not protein, carbohydrate or lipid

26Hershey & ChaseHershey & Chase

RadioactiveRadioactiveProteinProtein

Little Little RadioactivityRadioactivityin Offspringin Offspring

RadioactiveRadioactiveDNADNA

Most of the Most of the RadioactivityRadioactivityin Offspringin Offspring