Nucleotides and nucleic acids10/10/051Fig. 8-1, 8-19, 8-25Nucleotides are the building blocks of nucleic acidsNucleotides also play other important roles in the cellNucleotideDNARNA
Roles of nucleotides10/10/052• 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 enzymecofactors (NAD: nicotinamide adeninedinucleotide)
Roles of nucleic acids10/10/053• DNA contains genes, the information needed tosynthesize functional proteins and RNAs• DNA contains segments that play a role in regulation ofgene expression (promoters)• Ribosomal RNAs (rRNAs) are components of ribosomes,playing a role in protein synthesis• Messenger RNAs (mRNAs) carry genetic informationfrom a gene to the ribosome• Transfer RNAs (tRNAs) translate information in mRNAinto an amino acid sequence• RNAs have other functions, and can in some casesperform catalysis
Structure of nucleotides10/10/054 Fig. 8-1A phosphate groupNucleotides have three characteristic components:A nitrogenous base(pyrimidines or purine)A pentose sugar
Basic Structure of Nucleic AcidsMonophosphateDiphosphateTriphosphateAdenineGuanineThymineCytosineUracilNucleoside (Adenosine)Nucleotide (Adenosine monophosphate, AMP)PurinePyrimidine核苷核苷酸磷酸五環糖Ribose,Deoxyribose鹼基1’2’3’4’5’JuangRH(2004)BCbasics
Structure of nucleosides10/10/055Remove the phosphate group, and you have a nucleoside.H
ATP is a nucleotide - energy currency10/10/056∆G = -50 kJ/moltriphosphateBase (adenine)Ribose sugar
NAD is an important enzyme cofactor10/10/057Fig. 13-15NADH is a hydride transfer agent,or a reducing agent.Derived from Niacinnicotinamide
Nucleotides play roles in regulation10/10/058Fig. 6-30
Structure of nucleotides10/10/059Below is the general structure of a nucleotide. Thepentose sugar, the base, and the phosphate moietiesall show variations among nucleotides.Know this!
Ribose10/10/0511Fig. 8-3• Ribose (β-D-furanose) isa pentose sugar (5-membered ring).• Note numbering of thecarbons. In a nucleotide,"prime" is used (todifferentiate from basenumbering).51234
Ribose10/10/0512Fig. 8-3• An important derivative ofribose is 2-deoxyribose, orjust deoxyribose, in whichthe 2 OH is replaced withH.• Deoxyribose is in DNA(deoxyribonucleic acid)• Ribose is in RNA(ribonucleic acid).• The sugar prefersdifferent puckers in DNA(C-2 endo) and RNA C-3endo).
Pyrimidine and purine10/10/0514 Fig. 8-1Know these!Nucleotide bases in nucleic acids are pyrimidines or purines.
Pyrimidine and purine10/10/0515Nucleotide bases in nucleic acids are pyrimidines or purines.
Major bases in nucleic acids10/10/0516 Fig. 8-2• Among the pyrimidines, Coccurs in both RNA andDNA, but• T occurs in DNA, and• U occurs in RNAKnow these!• The bases areabbreviated by their firstletters (A, G, C, T, U).• The purines (A, G) occurin both RNA and DNA
Some minor bases10/10/0517Fig. 8-5• 5-Methylcytidine occurs in DNA of animals and higher plants• N6-methyladenosine occurs in bacterial DNAFig. 8-5
Variation in phosphate group10/10/05xFig. 8-6, 8-42• Adenosine 3, 5-cyclicmonophosphate (cyclic AMP,or cAMP) is an importantregulatory nucleotide.• In hydrolysis of RNA bysome enzymes,ribonucleoside 2,3-cyclicmonophosphates are isolableintermediates;ribonucleoside 3-monophosphates are endproducts• Another variation - multiplephosphates (like ATP).cAMP19 10/10/05
Nucleotides in nucleic acids10/10/0520• Bases attach to the C-1 of ribose or deoxyribose• The pyrimidines attach to the pentose via the N-1 position ofthe pyrimidine ring• The purines attach through the N-9 position• Some minor bases may have different attachments.
Deoxyribonucleotides10/10/0521Fig. 8-42-deoxyribose sugarDeoxyribonucleotides are abbreviated (for example) A, ordA (deoxyA), or dAMP (deoxyadenosine monophosphate)Phosphorylate the 5 positionand you have a nucleotide(here,deoxyadenylate ordeoxyguanylate)with a base (here, a purine,adenine or guanine)attached to the C-1position is adeoxyribonucleoside(here deoxyadenosine anddeoxyguanosine).
The major deoxyribonucleotides10/10/0522Fig. 8-4
Ribonucleotides10/10/0523 Fig. 8-4• The ribose sugar with abase (here, a pyrimidine,uracil or cytosine) attachedto the ribose C-1 positionis a ribonucleoside (here,uridine or cytidine).• Phosphorylate the 5position and you have aribonucleotide (here,uridylate or cytidylate)• Ribonucleotides are abbreviated (for example) U, or UMP(uridine monophosphate)
Nucleic acids10/10/0527 Fig. 8-7Nucleotide monomerscan be linked together via aphosphodiester linkageformed between the 3 -OHof a nucleotideand the phosphate of thenext nucleotide.Two ends of the resulting poly-or oligonucleotide are defined:The 5 end lacks a nucleotide atthe 5 position,and the 3 end lacks a nucleotideat the 3 end position.
Sugar-phosphate backbone10/10/0528Berg Fig. 1.1• The polynucleotide or nucleic acid backbone thus consists ofalternating phosphate and pentose residues.• The bases are analogous to side chains of amino acids; they varywithout 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.
The bases can take syn or anti positions10/10/0529 Fig. 8-18b
Sugar phosphate backbone conformation10/10/0530 Fig. 8-18a• Polynucleotides haveunrestricted rotation about mostbackbone bones (within limits ofsterics)• with the exception of the sugarring bond• This behavior contrasts with thepeptide backbone.• Also in contrast with proteins,specific, predictable interactionsbetween bases are often formed:A with T, and G with C.• These interactions can beinterstrand, or intrastrand.
Compare polynucleotides and polypeptides10/10/0531• As in proteins, the sequence of side chains(bases in nucleic acids) plays an importantrole in function.• Nucleic acid structure depends on thesequence of bases and on the type of ribosesugar (ribose, or 2-deoxyribose).• Hydrogen bonding interactions areespecially important in nucleic acids.
Interstrand H-bonding between DNA bases10/10/0532Fig. 8-11Watson-Crick base pairing
DNA structure determination10/10/0533• Franklin collected x-raydiffraction data (early 1950s)that indicated 2 periodicitiesfor DNA: 3.4 Å and 34 Å.• Watson and Crick proposed a 3-D model accounting for the data.
DNA structure10/10/0534Fig. 8-15• DNA consists of two helicalchains wound around thesame axis in a right-handedfashion aligned in anantiparallel fashion.• There are 10.5 base pairs, or36 Å, per turn of the helix.• Alternating deoxyribose andphosphate groups on thebackbone form the outsideof the helix.• The planar purine andpyrimidine bases of bothstrands are stacked insidethe helix.
DNA structure10/10/0535Fig. 8-15• The furanose ring usually ispuckered in a C-2 endoconformation in DNA.• The offset of therelationship of the base pairsto the strands gives a majorand a minor groove.• In B-form DNA (mostcommon) the depths of themajor and minor grooves aresimilar to each other.
Base stacking in DNA10/10/0536Berg Fig. 1.4; 5.13• C-G (red) and A-T (blue) basepairs are isosteric (same shapeand size), allowing stacking alonga helical axis for any sequence.•Base pairs stackinside the helix.
DNA strands10/10/0537Fig. 8-16• The antiparallel strands of DNA arenot identical, but are complementary.• This means that they are positionedto align complementary base pairs: Cwith G, and A with T.• So you can predict the sequence ofone strand given the sequence of itscomplement.• Useful for information storage andtransfer!• Note sequence conventionally is givenfrom the 5 to 3 end
B,A and Z DNA10/10/0538Fig. 8-19• B form - The most commonconformation for DNA.• A form - common for RNAbecause of different sugarpucker. Deeper minor groove,shallow major groove• A form is favored in conditionsof low water.• Z form - narrow, deep minorgroove. Major groove hardlyexistent. Can form for some DNAsequences; requires alternatingsyn and anti base configurations.36 base pairsBackbone - blue;Bases- gray
RNA has a rich and varied structure10/10/0540 Fig. 8-26Watson-Crick base pairs(helical segments;Usually A-form).Helix is secondarystructure.Note A-U pairs inRNA.DNA canformstructureslike this aswell.