5 Структура нуклеиновых кислот (1160074), страница 2
Текст из файла (страница 2)
12-5). The type of atom to which the substituent is attached (N, C, O, etc.) is not identified. The convention changeswhen the substituted atom is exocyclic, in which case the type of atomis identified and the ring position to which it is attached is denotedwith a superscript. The amino nitrogen attached to C-6 in adeninebecomes N6; similarly, the carbonyl oxygen and the amino group at C-6and C-2 of guanine become O6 and N2, respectively.
Examples of basessubstituted on exocyclic atoms are A^-methyladenine, and A^-methylguanine, as shown in Figure 12-5.Cells also contain nucleotides with phosphate groups in positionsother than on the 5' carbon (Fig. 12-6). Ribonucleoside 2',3'-cyclicFigure 12-5 Some minor purine and pyrimidinebases, (a) Minor bases found in DNA. 5-Methylcytosine occurs in the DNA of animals and higherplants, A^-methyladenine in bacterial DNA, and5-hydroxymethylcytosine in bacteria infected withcertain bacteriophages. (b) Some minor bases oftRNAs.
Note that pseudouracil is identical to uracil; the distinction is the point of attachment to theribose—uracil is attached through N-l, the normalattachment point for pyrimidines, and pseudouracilis attached through C-5.phosphates are intermediates and ribonucleoside 3'-phosphatesare end products of the hydrolysis of RNA by certain ribonucleases.Another variation is represented by adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP), considered at the end of this chapter.Figure 12-6 Some adenosine monophosphates.Adenosine 2'-monophosphate, 3'-monophosphate,and 2',3'-cyclic monophosphate are intermediates inthe alkaline hydrolysis of RNA.AdenineAdenine2'0OHOO—P—O"OH OHAdenosine 5'-monophosphateIIoAdenosine 2'-monophosphateOOHI"O—P—O"IIoAdenosine 3'-monophosphateOOAO0"Adenosine 2',3'-cyclicmonophosphate328RNADNA5' End5' EndPhosphodiester - Q ^ >==)bridgeIo5'CH2/OOOHO—P=OFigure 12-7 The covalent backbone structures ofDNA and RNA, showing the phosphodiester bridges(one of which is shaded in the DNA) linking successive nucleotide units.
The backbone of alternatingpentose and phosphate groups of both DNA andRNA is highly polar.OOHO-P=O3' End3' EndPhosphodiester Bonds Link SuccessiveNucleotides in Nucleic AcidsThe successive nucleotides of both DNA and RNA are covalently linkedthrough phosphate-group "bridges." Specifically, the 5'-hydroxyl groupof one nucleotide unit is joined to the 3'-hydroxyl group of the nextnucleotide by a phosphodiester linkage (Fig.
12-7). Thus the covalent backbones of nucleic acids consist of alternating phosphate andpentose residues, and the characteristic bases may be regarded as sidegroups joined to the backbone at regular intervals. Also note that thebackbones of both DNA and RNA are hydrophilic. The hydroxyl groupsof the sugar residues form hydrogen bonds with water. The phosphategroups in the polar backbone have a pK near 0 and are completelyionized and negatively charged at pH 7; thus DNA is an acid. Thesenegative charges are generally neutralized by ionic interactions withpositive charges on proteins, metal ions, and polyamines.Chapter 12 Nucleotides and Nucleic AcidsAll the phosphodiester linkages in DNA and RNA strands have thesame orientation along the chain (Fig.
12-7), giving each linear nucleicacid strand a specific polarity and distinct 5' and 3' ends. By definition,the 5' end lacks a nucleotide at the 5' position, and the 3' end lacks anucleotide at the 3' position (Fig. 12-7). Other groups (most often oneor more phosphates) may be present on one or both ends.The covalent backbone of DNA and RNA is subject to slow, nonenzymatic hydrolysis of the phosphodiester bonds.
In the test tube, RNAis hydrolyzed rapidly under alkaline conditions, but DNA is not; the2'-hydroxyl groups in RNA (absent in DNA) are directly involved in theprocess. Cyclic 2',3'-monophosphates are the first products of theaction of alkali on RNA, and are rapidly hydrolyzed further to yield amixture of 2'- and 3'-nucleoside monophosphates (Fig.
12-8).The nucleotide sequences of nucleic acids can be represented schematically, as illustrated (at right) by a segment of DNA having fivenucleotide units. The phosphate groups are symbolized by (P) and eachdeoxyribose by a vertical line. The carbons in the deoxyribose are represented from 1' at the top to 5' at the bottom of the vertical line (eventhough the sugar is always in its closed-ring /3-furanose form in nucleicacids). The connecting lines between nucleotides (through (P)) aredrawn diagonally from the middle (3') of the deoxyribose of one nucleotide to the bottom (5') of the next.
By convention, the structure of asingle strand of nucleic acid is always written with the 5' end at theleft and the 3' end at the right; i.e., in the 5'-*3' direction. Some simpler representations of the pentadeoxyribonucleotide illustrated arepA-C-G-T-AoH, pApCpGpTpA, and pACGTA. A short nucleic acid isreferred to as an oligonucleotide. The definition of "short" is somewhat arbitrary, but the term oligonucleotide is often used for polymerscontaining 50 or fewer nucleotides. A longer nucleic acid is called a3295' End3'EndOHpolynucleotide.O-P=O2',3'-CyclicmonophosphatederivativeH2OMixture of 2'- and3 '-monophosphatederivativesOBase3ORNAOHShortenedRNAFigure 12-8 Hydrolysis of RNA under alkalineconditions.
The 2' hydroxyl acts as a nucleophile inan intramolecular displacement, the 2',3'-cyclicmonophosphate derivative is further hydrolyzed togive a mixture of 2'- and 3'-monophosphate derivatives. DNA, which lacks 2' hydroxyls, is stableunder similar conditions.330Part II Structure and CatalysisThe Properties of Nucleotide Bases Affect theStructure of Nucleic AcidsThe bases have a variety of chemical properties that affect the structure, and ultimately the function, of nucleic acids. Free pyrimidinesand purines are weakly basic compounds, and are thus called bases.The purines and pyrimidines common in DNA and RNA are highlyconjugated molecules (see Fig.
12-2). This property has important effects on the structure, electron distribution, and light absorption ofnucleic acids. Resonance involving many atoms in the ring gives mostof the bonds a partially double-bonded character. One result is thatpyrimidines are planar molecules; purines are very nearly planar, witha slight pucker. Free pyrimidine and purine bases may exist in two ormore tautomeric forms depending upon the pH. Uracil, for example,occurs in lactam, lactim, and double lactim forms (Fig. 12-9). Thestructures of the purines and pyrimidines shown in Figure 12-2 arethe tautomers predominating at pH 7.0. Again as a result of resonance,all of the bases absorb UV light, and nucleic acids are characterized bya strong absorption at wavelengths near 260 nm (Fig.
12-10).The purines and pyrimidines are also hydrophobic and relativelyinsoluble in water at the near neutral pH of the cell. At acidic or alkaline pH the purines and pyrimidines become charged, and their solubility in water increases. Hydrophobic stacking interactions in whichtwo or more bases are positioned with the planes of their rings parallel(similar to a stack of coins) represent one of two important modes ofinteraction between two bases. The stacking involves a combination ofvan der Waals and dipole-dipole interactions between the bases.These base-stacking interactions help to minimize contact with waterand are very important in stabilizing the three-dimensional structureof nucleic acids, as described later. The close interaction betweenstacked bases in a nucleic acid has the effect of decreasing the absorption of UV light relative to a solution with the same concentration offree nucleotides.
This is called the hypochromic effect.The most important functional groups of pyrimidines and purinesare ring nitrogens, carbonyl groups, and exocyclic amino groups. Hydrogen bonds involving the amino and carbonyl groups are the secondimportant mode of interaction between bases. Hydrogen bonds be-OHoFigure 12-9 Tautomeric forms of uracil. At pH^.0, the lactam form predominates; the other formsoecome more prominent as pH decreases.figure 12—10 The absorption spectra of the common nucleotides and their molar absorption coefficients at 260 nm and pH 7.0 (e26o)- The spectra ofhe corresponding ribonucleotides and deoxyribonu•leotides, as well as the nucleosides, are essentiallyientical.
![](https://s.studizba.com/z.php?f=/templates/si/i/noavatar.png&w=100&h=100&t=1"){kind=avatar}
