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- 2014/2015 - 3D Structures of Biological
Macromolecules Part 3 Nucleic Acids
Jürgen Sühnel jsuehnel_at_fli-leibniz.de
Leibniz Institute for Age Research, Fritz Lipmann
Institute, Jena Centre for Bioinformatics Jena /
Germany
Supplementary Material www.fli-leibniz.de/www_bio
c/3D/
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Molecules of Life
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Nucleic Acids
DNA genomic information (nucleosomes,
chromatin) RNA messenger RNA, ribosomal RNA,
transfer RNA, ribozymes, small RNAs, noncoding
RNAs, RNAi (gene silencing), aptamers
(alternatives to antibodies) PNA peptide
nucleic acids mimic nucleic acids
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New Roles for RNA
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New Roles for RNA
Couzin J. Breakthrough of the year. Small RNAs
make big splash.Science. 2002, 298, 2296-2297.
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From Gene to Protein
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History
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History
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Nucleic Acid Structure
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Nucleobases
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Chain Direction in Nucleic Acids
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Chain Direction in Nucleic Acids
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Nucleic Acid Backbone
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Nucleic Acid Backbone Torsion Angles
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Ribonucleotides and Deoxyribonucleotides
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Nucleic Acid Base Pairs
The ten possible purine-pyrimidine base pairs.
Source Ignacio Tinoco, Jr. in Gesteland, R. F.
and Atkins, J. F. (1993) THE RNA WORLD. Cold
Spring Harbor Laboratory Press.
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Nucleic Acid Base Pairs
The seven possible homo-purine base pairs.
Source Ignacio Tinoco, Jr. in Gesteland, R. F.
and Atkins, J. F. (1993) THE RNA WORLD. Cold
Spring Harbor Laboratory Press.
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Nucleic Acid Base Pairs
The four possible hetereo-purine base pairs.
Source Ignacio Tinoco, Jr. in Gesteland, R. F.
and Atkins, J. F. (1993) THE RNA WORLD. Cold
Spring Harbor Laboratory Press.
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Nucleic Acid Base Pairs
The seven possible pyrimidine-pyrimidine base
pairs.
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DNA Hydration
www.lsbu.ac.uk/water/nucleic.html
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Nucleic Acid Base Pairs Water-mediated Pairs
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Nucleic Acid Base Pairs Water-mediated Pairs
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Nucleic Acid Base Pairs Water-mediated Pairs
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Nucleic Acid Base Pairs with C-HO/N Interactions
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Nucleic Acid Base Pairs with C-HO/N Interactions
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Non-Canonical Base Pair Database
http//prion.bchs.uh.edu/bp_type/
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Selected Base Triples
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Base Triples in tRNA
Base triads in the crystal structure of yeast
phenylalanine transfer RNA (PDB code 4tna).
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Base Tetrads in a DNA Tetraplex
Parallel-stranded DNA tetraplex formed from the
Tetrahymena telomeric sequence d(TTGGGGT)
solved by NMR spectroscopy (PDB code 139d). The
structure contains four stacked G-tetrads in the
center and additional T-tetrads.
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Base Polyads
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Base Polyads
Base triads and a heptad in the crystal structure
of a pseudoknot from beet western yellow virus
(BWYV) involved in frameshifting (PDB code
437d). The heptad is formed from two triads
linked by A25.
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HBexplore H-bond Analysis in Proteins and
Nucleic Acids
www.imb-jena.de/www_bioc/hbx/hbx.html
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Geometrical Parameters for Base Pairs in Nucleic
Acids
ndbserver.rutgers.edu/archives/report/tsukuba_sup/
bp_step_hel.html
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Nucleic Acid Structure
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Nucleic Acid Structure Sugar Conformation
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Nucleic Acid Structure Sugar Conformation
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Nucleic Acid Structure Sugar Conformation
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Nucleic Acid Structure
P         P is the pitch of the helix
corresponding to the distance between a base and
the base obtained after walking along the DNA
one full turn of 360. n         n is the number
on nucleotides within one pitch. h        
distance between base planes.
online-media.uni-marburg.de/chemie/bioorganic/vorl
esung1/kapitel1e.html?/chemie/bioorganic/vorlesung
1/k1e-20.html
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DNA Conformations
B
A
Z
www.rcsb.org/pdb/molecules/pdb23_3.html
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Ideal DNA Conformations and a Real B-DNA
Structure
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Nucleic Acid Conformations

• B-DNA is found at low salt concentrations. It is
  believed to be the native conformation occurring
  in chromatin.
• In the cell nucleus DNA is complexed with about
  an equivalent mass of protein to form a structure
  
• known as chromatin. Chromatin is a periodic
  structure made up of repeating, regularly spaced
• subunits, the subunit being the nucleosome.
  Within the nucleosomes the major part of DNA is
• wrapped around histones. The remaining DNA
  joining each nucleosome is known as linker DNA.
• A-DNA In solutions with higher salt
  concentrations or with alcohol added A-DNA is
  found.
• Z-DNA occurs for alternating poly(dG-dC)
  sequences in solutions with high salt
  concentrations or alcohol.
• RNA occurs (contrary to DNA) almost exclusively
  in the A-conformation (or in a related A'-form).
• There are further nucleic acid conformations
  like C-DNA, H-DNA or others which are not
  discussed
• here.
• Geometrical features
• The distance between two subsequent base pairs
  along the helical axis is called helical rise
  (h).
• The pitch (p) is the length of the helix axis
  for one complete helix turn.
• The turn angle per nucleotide or twist angle (t)
  is given by 360 / number of nucleotides per
  turn.
• C2'-endo and C3'-endo are descriptions of sugar
  conformations.
• The most frequently occurring nucleic acid model
  conformations are characterized by the following
  geometrical
• parameters

Groove width Groove depth
major minor major minor
A-DNA 2.7 Å 11.0 Å 13.5 Å 2.8 Å
B-DNA 11.7 Å 5.7 Å 8.5 Å 7.5 Å
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Nucleic Acid Conformations
Groove width Groove depth
major minor major minor
A-DNA 2.7 Å 11.0 Å 13.5 Å 2.8 Å
B-DNA 11.7 Å 5.7 Å 8.5 Å 7.5 Å
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Nucleic Acid Conformations - B-DNA
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Nucleic Acid Conformations - B-DNA
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Nucleic Acid Conformations B-DNA
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Nucleic Acid Conformations B-DNA
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First Single-crystal DNA Structure (B-DNA)
Drew-Dickerson structure
H. R. Drew, R. M. Wing, T. Takano, C. Broka, S.
Tanaka, K. Itakura, R. E. Dickerson Structure Of
A B-/DNA Dodecamer. Conformation And Dynamics
Proc. Nat. Acad. Sci. Usa V. 78 2179 1981
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Diversity of DNA Structures
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Nucleosome Core Particle (1aoi)
DNA in chromatin is organized in arrays of
nucleosomes.Two copies of each histone protein,
H2A, H2B, H3 and H4, Are assembled into an
octamer that has 145-147 base pairs of DNA
wrapped around it to form a nucleosome core.
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Integration Host Factor (1ihf)
An architectural protein which assists formation
of high order protein-DNA complexes such as
those found in replication and long distance
transcription regulation.
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CURVES
www.ibpc.fr/UPR9080/Curonline.html
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Integration Host Factor (1ihf) CURVES Output
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Integration Host Factor (1ihf) CURVES
Output Local Bending Analysis
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Integration Host Factor (1ihf) Local Bending
Analysis
Dinucleotide steps with unusual large values of
the roll and tilt angle are indicated in red.
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Integration Host Factor (1ihf) Global Bending
Analysis
Coordinate system and helical axis
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Integration Host Factor (1ihf) Global Bending
Analysis
Coordinate system and helical axis
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Integration Host Factor (1ihf) Global Bending
Analysis
Coordinate system and helical axis
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Integration Host Factor (1ihf) Globale Bending
Analysis
Coordinate system and helical axis
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Integration Host Factor (1ihf) Global Bending
Analysis
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Integration Host Factor (1ihf) Global Bending
Analysis
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Nucleic Acid Structure - Bending
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Cover Images for all 2003-2011 Issues of the
Journal RNA
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Large Ribosomal Subunit (1jj2) - 2001
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Jena Structures 5S rRNA E-loop/L25 complex
(1d6k)
IMB/FLI Molecular Biophysics/NMR Spectroscopy
(M. Görlach)
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Aptamers
Aptamers are DNA or RNA molecules that have been
selected from random pools based on their
ability to bind other molecules. Aptamers have
been selected which bind nucleic acid, proteins,
small organic compounds. These novel molecules
have many potential uses in medicine and
technology.
The Aptamer Database is a comprehensive,
annotated repository for information about
aptamers and in vitro selection. This resource is
provided to collect, organize and distribute all
the known information regarding aptamer
selection. http//aptamer.icmb.utexas.edu
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Aptamers
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Aptamer Structures
Nf-Kappa B (P50)2 Complexed To A High-Affinity
RNA Aptamer
PDB code 1ooa
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Aptamer Structures
RNA aptamer complex with arginine
PDB code 1koc
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Aptamer Structures
RNA aptamer complex with tobramycin
www.mpibpc.gwdg.de/inform/MpiNews/cientif/jahrg6/2
.00/fig4.html
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Aptamer Structures
RNA aptamer complex with tobramycin
PDB code 1tob
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Aptamer Structures
RNA aptamer complex with tobramycin
PDB code 1tob
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Cloverleaf Structure of tRNA
www.mona.uwi.edu/biochem/courses/
dd120/documents/
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t-RNA (4tna) - 1978
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Pseudoknots
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Chemical Structures of DNA and PNA
http//www.bentham.org/coc-sample/ganesh/ganesh.ht
m
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RNA/PNA Complex
S. C. Brown, S. A. Thomson, J. M. Veal, D. G.
Davis NMR Solution Structure Of A Peptide
Nucleic Acid Complexed With RNA Science V. 265
777 1994
PDB code 176d