Figure 5-11Three-dimensional structure of B-DNA.

Figure 5-12 Watson-Crick base pairs.

http://rutchem.rutgers.edu/~xiangjun/3DNA/images/bp_step_hel.gif

Twist varies with sequence.

Note:

importance of sequence > importance of composition.

Figure 29-7 The conformation of a nucleotide unit is determined by

the seven indicated torsion angles.

Figure 29-9b Sugar ring pucker. (b) The steric strain resulting in

Part a is partially relieved by ring puckering in a half-chair

conformation in which C3 is the out-of-plane atom.

Table 4.T02: Comparison of Major Features in A-, B-, and Z-Forms of DNA

Adapted from Ussery, D. W. Encyclopedia of Life Sciences. John Wiley & Sons, Ltd., May 2002. [doi: 10.1038/npg.els.0003122].

Table 29-1 Structural Features of Ideal A-, B-, and Z-DNA.

Figure 29-10aNucleotide sugar conformations. (a) The C3-endo conformation (on the same side of the sugar ring as C5), which occurs in A-

RNA and RNA-11.

Figure 29-10bNucleotide sugar conformations. (b) The C2-endo conformation,

which occurs in B-DNA.

Greater flexibility of B-DNA allows it to exhibit significant variation in the configuation of its sugar pucker under in vivo conditions. But see: http://www.chem.qmul.ac.uk/iupac/misc/pnuc2.html

From: http://www.chem.qmul.ac.uk/iupac/misc/pnuc2.html

Figure 4.05a: Deoxyguanylate in B-DNA in anti conformation

Figure 4.05b: Deoxyguanylate in Z-DNA in syn conformation

Figure 29-1a Structure of B-DNA. (a) Ball and stick drawing and corresponding space-filling model viewed perpendicular to the helix

axis.

~10 bp/turn- right handedPitch of 34 AngstromsWide major grooveNarrow minor

grooveStructure adopted byReal DNA deviates from

ideal structure in a

sequence-specific

manner.

Figure 4.04a: The C2’-endo conformation

Adapted from Voet, D., and Voet, J. G. Biochemistry, Third Edition. John Wiley & Sons, Ltd., 2005.

Figure 4.04b: The C3’-endo conformation

Adapted from Voet, D., and Voet, J. G. Biochemistry, Third Edition. John Wiley & Sons, Ltd., 2005.

Figure 29-1b Structure of B-DNA. (b) Ball and stick drawing and corresponding space-

filling model viewed down the helix axis.

Figure 4.01a: A-DNA

Protein Data Bank ID: 213D. Ramakrishnan, B., and Sundaralingam, M., Biophys. J. 69 (1995): 553-558 (top).

Figure 29-2a Structure of A-DNA. (a) Ball and stick drawing and corresponding space-filling model viewed perpendicular to the helix

axis.

11.6 bp/turn- right handedPitch of 34 AngstromsDeep major grooveVery shallow minor

grooveStructure adopted byA-RNA (aka. RNA-11)

Figure 29-2b Structure of A-DNA. (b) Ball and stick drawing and corresponding space-

filling model viewed down the helix axis.

Figure 4.01b: B-DNA

Protein Data Bank ID: 1BNA. Drew, H. R., et al., Proc. Natl. Acad. Sci. USA 78 (1981): 2179-2183 (middle).

Figure 29-3a Structure of Z-DNA. (a) Ball and stick drawing and corresponding space-filling model viewed perpendicular to the helix axis.

12 bp/turn- left-handed helixPitch of 44 AngstromsNo major grooveDeep minor grooveStructure adopted byAlternating Purine-

Pyrimidine pairs

(e.g., repeats of 2 bases pairs)Methylation of C favors

formation, as does

high salt conc.Genetic switch?

Figure 29-3b Structure of Z-DNA. (b) Ball and stick drawing and corresponding space-

filling model viewed down the helix axis.

Figure 4.01c: Z-DNA

Protein Data Bank ID: 2ZNA. Wang, A. H. J., et al. (bottom).

Figure 4.02a: Z-DNA with zig-zag sugar phosphate backbone shown in white

Protein Data Bank ID: 2ZNA. Wang, A. H. J., et al.

Figure 4.02b: The same Z-DNA with the zigzag sugar phosphate backbone shown in space filling display

Protein Data Bank ID: 2ZNA. Wang, A. H. J., et al.

Figure 29-4 Conversion of B-DNA to Z-DNA.

Base pairs flipped by 180 degrees

Repeat is d(pXpY)

Polyd(GC)-polyd(GC)

Polyd(AC)-polyd(GT)

Anti-C or T

Syn-G or A

May form transiently behind actively transcribing RNA polymerase

Figure 29-5 X-Ray structure of two ADAR1 Z domains in complex with Z-DNA.

Thought to targeted to Z-DNA upstream of actively transcribing genes

Figure 4.03: Drosophila (fruit fly) chromosomes with bound antibody to Z-DNA.

Reproduced from Nordheim, A., et al., Nature 294 (1981): 417-422. Photo courtesy of Alexander Rich, Massachusetts Institute of Technology.

Forces stabilizing nucleic acid structure

BASE PAIRING1) Geometric complementarity2) Electronic complementarity

Book: contribute -2 to -8 kJ/mol of base pairOther sources:A=U/A=T -5 to -9 kJ/mol of bpG=C -13 to -21 kJ/ mol of bpBase pairs replaced by H-bonds to water of nearly equivalent strength when DNA is denatured.Non Watson-Crick H-bonding have little stability

in dsDNAHowever, they do stabilize tertiary structure of tRNAs and have other roles (e.g., wobble base pairing in codon/anti-codon recognition.

Forces stabilizing nucleic acid structure

BASE STACKING1) Van der Waals radii

of aromatic ring ~1.7 angstroms

2) Adjacent bases 3.4 angstroms apart in helix

3) Contribute -4 kJ/mol

4) Base stacking is responsible for the hyperchromic effect observed when dsDNA is denatured

Forces stabilizing nucleic acid structure

HYDROPHOBIC FORCES1) Sugar-phosphates

on outside interacting with water.

2) Hydrophobic bases in interior

3) Base stacking is enthalpically driven and entropically opposed

4) Hydrophobic forces poorly understood

5) Increases in ionic strength stabilizes dsDNA and dsRNA.

Table 4.T01: Sizes of Various DNA Molecules

Figure 4.08: DNA melting curve.

Figure 4.09: Effect of G-C content on DNA melting temperature.

Figure 4.10: Several effects of cooperativity of base-stacking.

Figure 4.11: The effect of lowering the temperature to 25°C after strand separation has taken place.

Figure 4.06a: Inverted repeats

Adapted from Bacolla, A., and Wells, R. D., J. Biol. Chem. 279 (2004): 47411-47414.

Figure 4.06b: Cruciform structure

Adapted from Bacolla, A., and Wells, R. D., J. Biol. Chem. 279 (2004): 47411-47414.

Figure 4.07: Hairpin RNA.

Adapted from Horton, R. H., et al. Principles of Physical Biochemistry, Second Edition. Prentice Hall, 2006.

Hyperchromic effect- increase of 1.4xA260 upon denaturation of double-stranded nucleic Acids (dsDNA or dsRNA

Forces stabilizing nucleic acid structure

IONIC INTERACTIONS1. Electrostatic

repulsion of phosphates destabilize dsDNA structure

2. Effect counteracted or stabilized by cations-Metal ions: Na+, K+,

Mg2+

-polyamines-basic proteins-Mg2+ effect 100-

1000X of Na+ ions.

ENTROPICALLY UNFAVORABLE1) Highly ordered2) Increase temperature= decrease stabilityTm=41.1XG+C + 16.6log[Na+] +81.5