DNA

CONFORMATION
ANDRIANI

Department Biochemistry and Molecular Biology Faculty of Medicine Tanjungpura University

PREFACE..

Linus Pauling

In the early 1950s, he proposed that regions of protein can fold into a secondary structure

a-helix

To elucidate this structure, he built ball-and-stick models

Refer to Figure 9.12b

Rosalind Franklin

She worked in the

same laboratory as Maurice Wilkins

The diffraction pattern she obtained suggested several structural features of DNA

Helical More than one strand 10 base pairs per complete turn

The diffraction pattern is interpreted (using mathematical theory) This can ultimately provide information concerning the structure of the molecule

Erwin Chargaffs Experiment

Interpreting the Data

The compelling observation was that

Percent of adenine = percent of thymine Percent of cytosine = percent of guanine

This observation became known as Chargaffs rule

It was crucial evidence that Watson and Crick used to elucidate the structure of DNA

Watson and Crick

Stick and ball experimental for DNA conformation A critical question was how the two (or more strands) would interact An early hypothesis proposed that the strands interact through phosphate-Mg++ crosslinks

Watson and Crick

They then built models with the

Sugar-phosphate backbone on the outside Bases projecting toward each other

They first considered a structure with identical bases in the opposite strand

ie., A to A, T to T, C to C, and G to G

They then realized that the hydrogen bonding of A and T resembled that between C and G

 Watson dan Crick (1953)

Model struktur DNA : double helix

BASE PAIRING
ikatan hidrogen bukan ikatan kovalen Stabilitas DNA ditentukan oleh pH, kadar garam, suhu, dan kadar pasangan basa G-C

STRUKTUR NUKLEOTIDA
Nukleosida : gula + basa Nukleotida : Nukleosida + fosfat

STRUKTUR DOUBLE HELIX MERUPAKAN POLINUKLEUTIDA ANTIPARALEL

The DNA Double Helix

the minor groove, is 12 wide the major groove, is 22 wide

DUA POLINUKLEOTIDA BERIKATAN ANTIPARALEL MEMBENTUK STRUKTUR DOUBLE HELIX DNA

G

STRUKTUR ALTERNATIF KONFORMASI DNA

Tiga jenis bentuk putaran double helix DNA 1 basa berputar 36 10 basa = 360

1. 2. 3.

DNA tipe B DNA tipe A DNA tipe Z

Right handed DNA Paling banyak Right handed DNA ditemukan di dalam 11pb/putaran sel Lebih kompak Left handed DNA 10pb/putaran Central pore Zigzag appearance dibagian bawah

DNA TIPE A

DNA TIPE B

DNA TIPE Z

Bases substantially tilted relative to the central axis

Bases substantially tilted relative to the central axis

Bases relatively perpendicular to the central axis Sugar-phosphate backbone follows a zigzag pattern

Its formation is favored by

GG-rich sequences, at high salt concentrations Cytosine methylation, at low salt concentrations

In the late 1950s, Alexander Rich et al discovered triplex DNA

T binds to an AT pair in biological DNA

Triplex DNA formation is sequence specific The pairing rules are

Triplex DNA has been implicated in several cellular processes

C binds to a CG pair in biological DNA

Replication, transcription, recombination

Cellular proteins that specifically recognize triplex DNA have been recently discovered

VARIASI STRUKTUR DNA

Pasangan Tipe Untaian Basa/Putaran
Rotasi/Pasa ngan Basa

Diameter Untaian

Kondisi Terjadinya Kelembapan relatif Dalam Larutan

A B

11 10

+32,7 +36,0

23 A 19 A

75 % 92 %

K+, Na+, Kadar Garam Rendah Kadar Garam Tinggi

C Z

9,33 12

+38,6 -30,0

19 A 18 A

66 % -

Ribonucleic acid (RNA)

STRUKTUR RNA
Complementary regions Held together by hydrogen bonds

RNA single strand RNA double strand

Noncomplementary regions Have bases projecting away from double stranded regions

Also called hair-pin

STRUKTUR RNA
PSEUDOKNOT
Pseudoknot dibentuk oleh pasangan basa antara sekuens yang saling komplementer

Mengapa DNA Lebih Stabil dibanding RNA?

Ada tidaknya ikatan hidrogen antara untai yang

berlawanan
Ada tidaknya pengaruh tumpukan pasangan basa satu

sama lain yang berinteraksi

Ikatan phospohodiester sebagai backbone structure

orientasi single strand

A-Form DNA vs B-Form DNA

Tipe B 1. Pada kadar garam rendah tipe A 2. Pada kadar garam tinggi tipe Z
Pembentukan double strand dari single strand:

1. H RNA = 40 kJ/mol per bp; S RNA = 105 J/mol per bp 2. H DNA = 35 kJ/mol per bp; S DNA = 90 J/mol per bp
Kestabilan konformasi DNA tipe A dan B bukan karena

gula ribosanya, melainkan krn konformasinya

Many factors contribute to the tertiary structure of RNA

For example

Molecule contains single- and doublestranded regions These spontaneously interact to produce this 3-D structure

Base-pairing and base stacking within the RNA itself Interactions with ions, small molecules and large proteins

depicts the tertiary structure of tRNAphe

The transfer RNA that carries phenylalanine

Structural features of the three major forms of DNA (Wikipedia)

Geometry attribute Helix sense Repeating unit Rotation/bp bp/turn Inclination of bp to axis Rise/bp along axis Pitch/turn of helix Mean propeller twist Glycosyl angle Sugar pucker Diameter A-DNA right-handed 1 bp 32.7 11 +19 2.3 (0.23 nm) 28.2 (2.82 nm) +18 anti C3'-endo 23 (2.3 nm) B-DNA right-handed 1 bp 35.9 10.5 1.2 3.32 (0.332 nm) 33.2 (3.32 nm) +16 anti C2'-endo 20 (2.0 nm) Z-DNA left-handed 2 bp 60/2 12 9 3.8 (0.38 nm) 45.6 (4.56 nm) 0 C: anti, G: syn C: C2'-endo, G: C2'-exo 18 (1.8 nm)

DNA TIPE B
memiliki major groove dan minor groove struktur yang dikemukakan oleh Watson dan Crick
Ditemukan lebih banyak pada kondisi fisiologis

DNA TIPE A
Major groove lebih besar Biasanya terdapat pada tRNA dan hibrid DNA-RNA

DNA TIPE Z
kerangka gula-posfat berbentuk zigzag rangkaian basa G-C dan A-C yang berulang ditemukan pada kondisi fisiologis jika termetilasi pada basa Cytosin Lebih bermuatan negatif

Ribonucleic acid (RNA)

Rantai belakang glukosa= Ribosa

Basa Urasil menggantikan Timin

Fungsi RNA: 1. Materi geentik (virus) 2. Bertindak sebagai molekul intermediate (mRNA), adaptor (tRNA), struktur (rRNA) and katalis (ribozime)

The Data