Figure 5-12
WatsonCrick base pairs.
Figure 5-11
Threedimensional
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 29-10a
Nucleotide 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 29-10b
Nucleotide sugar
conformations. (b) The C2-endo
conformation, which occurs in BDNA.
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
~10 bp/turn- right handed
Pitch of 34 Angstroms
Wide major groove
Narrow minor
groove
Structure adopted by
Real DNA deviates from
ideal structure in a
sequence-specific
manner.
Figure 29-1a
Structure of B-DNA. (a) Ball
and stick drawing and corresponding spacefilling model viewed perpendicular to the helix
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 spacefilling 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).
11.6 bp/turn- right handed
Pitch of 34 Angstroms
Deep major groove
Very shallow minor
groove
Structure adopted by
A-RNA (aka. RNA-11)
Figure 29-2a
Structure of A-DNA. (a) Ball
and stick drawing and corresponding spacefilling model viewed perpendicular to the helix
Figure 29-2b
Structure of A-DNA. (b) Ball
and stick drawing and corresponding spacefilling 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).
12 bp/turn- left-handed helix
Pitch of 44 Angstroms
No major groove
Deep minor groove
Structure adopted by
Alternating PurinePyrimidine pairs
(e.g., repeats of 2
bases pairs)
Methylation of C favors
formation, as does
high salt conc.
Genetic switch?
Figure 29-3a Structure of Z-DNA. (a) Ball and stick drawing and
corresponding space-filling model viewed perpendicular to the helix axis.
Figure 29-3b
Structure of Z-DNA. (b) Ball
and stick drawing and corresponding spacefilling 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.
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 29-4
Conversion of B-DNA to ZDNA.
Thought to targeted to Z-DNA upstream of actively transcribing genes
Figure 29-5
X-Ray structure of two ADAR1
Z domains in complex with Z-DNA.
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 PAIRING
1) Geometric complementarity
2) Electronic complementarity
Book: contribute -2 to -8 kJ/mol of
base pair
Other sources:
A=U/A=T -5 to -9 kJ/mol of bp
G=C -13 to -21 kJ/ mol of bp
Base pairs replaced by H-bonds to
water of nearly equivalent strength
when DNA is denatured.
Non Watson-Crick H-bonding have little stability in dsDNA
However, 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 STACKING
1) 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 FORCES
1) 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 INTERACTIONS
1. 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 UNFAVORABLE
1) Highly ordered
2) Increase temperature= decrease stability
Tm=41.1XG+C + 16.6log[Na+] +81.5