namedanny van noort officeroom 410 building#139 (ict) tel:880 9131 [email protected] web where...
TRANSCRIPT
name danny van noort
Office Room 410
building #139 (ICT)
tel: 880 9131
email [email protected]
web http://bi.snu.ac.kr/
Where to find me
Biochemistry part 1
1 Introduction
2 Theoretical backgroundBiochemistry/molecular biology
3 Theoretical backgroundcomputer science
4 History of the field
5 Splicing systems
6 P systems
7 Hairpins
8 Micro technology introductions Microreactors / Chips
9 Microchips and fluidics
10 Self assembly
11 Regulatory networks
12 Molecular motors
13 DNA nanowires
14 Protein computers
15 DNA computing - summery
Course outline
Popular books
More popular books
Very short introduction
ATOM
MOLECULE
CELL
ORGANISM
SPECIES
Physical
Chemical
Biological
Physiological
Ecological
Biological background
Role of molecules in cells
Perform various chemical reactions necessary for
life => diverse 3D structures necessary
Pass on the instructions for making an organism
=>simple 1D medium sufficient
Types of molecules in cells
Proteins: 3D structures
DNA: 1D medium
RNA: intermediary between DNA and proteins
Molecular biology concepts
Cells
Humans
60 trillion cells
320 cell types
Classified into two types:
Eukaryotes contain a membrane-bound nucleus and
organelles (plants, animals, fungi,…)
Prokaryotes lack a true membrane-bound nucleus and
organelles (single-celled, includes bacteria)
Not all single celled organisms are prokaryotes!
Organisms
• In eukaryotes, nucleus contains one or several double
stranded DNA molecules organized as chromosomes
• Humans:
– 22 Pairs of autosomes
– 1 pair sex chromosomes
Chromosomes
Chromosomes
DNA RNA protein
Central dogma
transcription translation
deoxyribonucleic acid
The sequence of the human genome
has 2.91 billion base pairs (bp)
and approximately 35,000 genes.
(last count 2003)
DNA (deoxyribonucleic acid)
DNA (deoxyribonucleic acid)
Watson & Crick (1953): Nature 25: 737-738
Molecular Structure of Nucleic Acids: a
structure for deoxyribose nucleic acid.
Nobel Prize, 1962.
Nucleotide: purine or pyrimidine base deoxyribose sugar phosphate group
Purine bases A(denine), G(uanine)
Pyrimidine bases C(ytosine), T(hymine)
DNA (deoxyribonucleic acid)
Nitrogenous Base
34 Å
MajorGroove
Minor Groove
Central Axis
Sugar-PhosphateBackbone
20 Å 5’ C 3’ OH
3’ 0H C 5’
5’
3’
3’
5’
Structure of DNA
Adenine Thymine
to Sugar-PhosphateBackbone
to Sugar-PhosphateBackbone
(+) (-)
(+)(-)
Hydrogen Bond
Guanine Cytosine
to Sugar-PhosphateBackbone
to Sugar-PhosphateBackbone
(-) (+)
(+)(-)
(+)(-)
Inter-strand hydrogen bonding
20
Watson-Crick complement
Inter-strand hydrogen bonding
Structure and Nomenclature of Nucleotides
Nitrogenous Bases
N
N NH
N
NH2
HN
N NH
N
O
H2N
N
NH
NH2
O
NH
NH
O
O
NH
NH
O
O
N
N NH
N
N
N
1
2
34
56 7
8
9
1
2
34
5
6
Adenine(6-amino purine)
Guanine (2-amino-6-oxy purine)
Cytosine (2-oxy-4-amino pyrimidine)
Thymine (2-oxy-4-oxy 5-methyl pyrimidine)
Uracil(2-oxy-4-oxypyrimidine)
purine
pyrimidine
Nucleic acids are polynucleotides;
Nucleotides are linked by phosphodiester bridges from
3’ to 5’;
Polymers of ribonucleotides are ribonucleic acids, or
RNA;
Polymers of deoxyribonucleotides are deoxyribonucleic
acids, or DNA;
Structure of DNA
Sugar backbone
N
NN
N
NH2
O
OHO
HHHH
PO
O
O
O-
NH
N
N
O
NH2N
O
OH
HHHH
O
PO
-O
O-
5’
3’
P P
T
P
A
P
G
P
C
OH
C
5’
3’
Shorthand notation of a nucleic acid
Structure of DNA
5’ GTAAAGTCCCGTTAGC 3’
Single stranded polynucleotide
5’ GTAAAGTCCCGTTAGC 3’| | | | | | | | | | | | | | | |3’ CATTTCAGGGCAATCG 5’
Double stranded polynucleotide
27
The B-form is the common
natural form, prevailing
under physiological
conditions of low ionic
strength and high degree
of hydration.
The Z-form (Zigzag chain)
is observed in DNA G-C
rich local region.
The A-form is sometimes
found in some parts of
natural DNA in presence
of high concentration of
cations or at a lower
degree of hydration
(<65%).
Structure of DNA
Central dogma
DNA RNA protein
Central dogma
transcription translation
Replication of DNA
Replication of DNA
Replication of DNA
During replication, the DNA helix is unraveled and its two
strands are separated. An area known as the replication
bubble forms and progresses along the molecule in both
direction. Then each DNA strand serves as a template for the
synthesis of a new complementary strand.
Each daughter DNA molecule is an exact copy of its parent
molecule, consisting of one old and one new DNA strand. Thus
the replication is semi-conservative
A B
a b
A B
a b
b
B
a
A
HEAT
COOL
ba
A BOR
100° C
Strand hybridisation
’ ’
’ ’
Ligase joins 5' phosphate to 3' hydroxyl
’ ’
DNA ligation
EcoRI
HindIII
AluI
HaeIII
- OH 3’
5’ P -
- P 5’
3’ OH -
Restriction endonucleases
DNA polymerase
ribonucleic acid
Similar to DNA
Thymine (T) is replaced by uracil (U)
Forms secondary or tertiary structures
RNA can be:
Single stranded
Double stranded
Hybridized with DNA
RNA (ribonucleic acid)
Types of RNAs:
Transfer RNA (adaptor molecule)
Messenger RNA (template for protein synthesis)
Ribosomal RNA (protein synthesis)
Small nuclear RNA (splicesomal RNA)
Small nucleolar RNA (ribosomal RNA processing)
Interference RNA (gene silencing)
microRNA (translation regulation)
Virus RNA (code virus genome)
In comparison with DNA structures, much less is known
about RNA structures. Most RNA are associated with
proteins which facilitate their structural folding.
RNA (ribonucleic acid)
RNA secondary structure
Messenger RNA
Linear molecule encoding genetic information
copied from DNA molecules
Transcription: process in which DNA is copied
into an RNA molecule
mRNA
Eukaryotic genes can be pieced together
Exons: coding regions
Introns: non-coding regions
mRNA processing removes introns, splices
exons together
Processed mRNA can be translated into a
protein sequence
mRNA processing
Parts List:
mRNA is template
tRNA
ribosomes
amino acids
aminoacyl tRNA transferases
mRNA processing
mRNA processing
Transcription
Scientists first 3-D pictures of
the "heart" of the transcription
machine.
Ban et al., Science 289 (905-920), 2000
Secondary StructureOf large ribosomal RNA
Tertiary StructureOf large ribosome subunit
Ribosomal RNA
Translation
Translation
Transfer RNA
Well-defined three-dimensional structure
Critical for creation of proteins
tRNA
Amino acid attached to each tRNA
Determined by 3 base anticodon sequence (complementary
to mRNA)
Translation: process in which the nucleotide sequence
of the processed mRNA is used in order to join amino
acids together into a protein with the help of
ribosomes and tRNA
tRNA
tRNA structure
AnticodonStem
D Loop
TyC Loop
Variableloop
Anticodon Loop
Secondary Structure Of large ribosomal RNA
Tertiary StructureOf large ribosome subunit
tRNA structure
Translation codons
Translation initiation
Translation elongation
Translation termination
Translation codons