Download
1 / 103
1.04k likes | 1.19k Vues
BIOCHEMISTRY Chapter 2. NEUCLEIC ACIDS Teacher: Xiaoli Zheng. CONTENTS. 1 DNA is a biopolymer molecular composed of deoxyribonucleotides through phosphodiester bonds. Primary structure: nucleotide sequence; Secondary structure: right-handed double helix.
E N D
BIOCHEMISTRYChapter 2 NEUCLEIC ACIDS Teacher: Xiaoli Zheng
CONTENTS 1 DNA is a biopolymer molecular composed of deoxyribonucleotides through phosphodiester bonds. Primary structure: nucleotide sequence; Secondary structure: right-handed double helix. A DNA molecular: two antiparallel strands wound together around one axis through hydrogen bond interaction. Hydrogen bonds: formed between complementary base pairs (A-T, G-C)
CONTENTS 2 RNA: also a biopolymer molecular; RNA is composed of ribonucleotides and exists in a single-strand form in general (different from DNA). RNA: mRNA, tRNA, rRNA
CONTENTS 3 A double-stranded DNA molecular can be denatured at high temperature. Separated single-stranded DNA molecules can be renatured when the denature condition are removed.
Nucleic acid, like protein, is a kind of biological macromolecule.
ribocucleic acid deoxyribocucleic acid
DNA: nucleus and mitochondrion Carries genetic information which determines the genotype of the cells and individuals.
RNA: nucleus, mitochondrion and cytoplasm Paticipates in the biosynthesis of polypeptides or proteins according to the genetic information transferred from DNA.
Ribose or deoxyribose (RNA DNA) 1.1 Nucleotides Nucleotides = Base + Pentose+ Phosphate
Nitrogen-containg cyclic compound Two types of bases Purine bases adenine（腺嘌呤） guanine（鸟嘌呤） Pyrimidine Bases uracil（尿嘧啶） cytosine（胞嘧啶） thymine（胸腺嘧啶）
DNA: A T G C • RNA: A U G C
adenine（腺嘌呤） The atoms of these bases are labled numerically. The carbonyl and amino groups of purines and pyrimidines exhibit keto-enol and amine –iminetautomerism under the influence of pH, which provides the basis for hydrogen bond formation in nucleic acid.
Tautomerization of the bases • The bases can tautomerize; that is, the bases can redistribute positions of hydrogens and double bonds
5’ 1’ Pentose 4’ 2’ 3’ DNA:β-D-2’-deoxyribose (Hydrogen ) RNA: β-D-ribose (Hydroxyl) DNA is chemically more stable than RNA due to the structural distinction of pentose, making the nature select DNA as the genetic information carrier.
Nucleoside β-D-glycosidic bond A base A ribose N-9-atom of purine or N-1-atom of pyrimidine C-1’ atom of pentose (no phosphate)
Deoxynucleoside β-D-glycosidic bond A base A deoxyribose N-9-atom of purine or N-1-atom of pyrimidine C-1’ atom of pentose (no phosphate)
The glycosidic bonds in DNA and RNA are predominantly in the anti conformation due to the steric effect. • http://science.uvu.edu/ochem/index.php/alphabetical/a-b/anti-conformation/
Nucleotide Phosphoryl group phosphoesterified Phosphoester bond Nucleoside (5’-OH, 5’- Hydroxyl) β-D-glycosidic bond A base A ribose
Standard Nucleotides： • 5’- adenosine monophosphate 5’-AMP • 5’- guanosine monophosphate 5’-GMP • 5’- cytidine monophosphate 5’-CMP • 5’- uridine monophosphate 5’-UMP • 5’- deoxyadenosine monophosphate 5’-dAMP • 5’- deoxyguanosine monophosphate 5’-dGMP • 5’- deoxycytidine monophosphate 5’-dCMP • 5’-deoxythymidine monophosphate） 5’-dTMP
Nucleotides and deoxynucleotides may have diffenrent phosphateforms. 5’- deoxyadenosine monophosphate 5’-dAMP 5’- deoxyadenosine diphosphates 5’-dADP 5’- deoxyadenosine triphosphates 5’-dATP
1.2 Nucleotides have different derivatives Cyclic Nucleotides The phosphate group of nucleotides monophosphate can react with 3’-OH group of itself to form a circular phosphate substance like cyclic AMP (cAMP) and cyclic GMP (cGMP). They are important secondary messengers in signal transduction. ATP and UTP are the substrates or the intermediary products in the energy metabolic process.
1.3 Polynucleotide is formed when many nucleotides are linked together. The 5’-phosphate group of a nucleotide can react with the 3’-OH group of another nucleotide to form a covalent bond called phosphodiester bond. Continuation of such esterification reactions forms a linear polynucleotide chain. Directional: (5’---3’)a free phosphate group at the 5’-end and a free hydroxyl group at the 3’-end.
1.4 Primary Structure of Polynucleotides • The primary structure (DNA or RNA): defined as its nucleotide sequence or its base sequence. • Directionality ：5’3’ Size :base-pair (bp) kilobase-pair (kbp) A DNA molecule of n nucleotides has 4n possible combinations, providing a great potential for genetic information storage.
Significance of Primary Structure • Genetic information stored in nucleotide sequence of DNA • Gene is a particular DNA sequence
Primary structure Structure Secondary structure Spatial structure Higher structure
2.1 Secondary structure of DNA • The secondary structure refers to the shape a nucleic acid assumes as a result of the primary structure. relative positions of all atoms of DNA molecule
1953, James Waston and Francis Crick,secondary structure of DNA
a. The two chains in the double helix are antiparallel. The two strands are wound together into a right-handed helix around a common axis. d= 2 nm, pitch = 3.4 nm, 10.4 bp / turn of the helix pitch diameter
b. The hydrophilic backbone of the two strands lie on the surface of the helix, and the hydrophobic base are buried inside the helix.
c. These two strands are held together by hydrogen bonds formed between bases in the antiparallel strands. The bases on the two chains pair in a complementary fashion. A=T，G=C.
d. The base pair lie perpendicular to the helical axis, and one base pair stacks on the top of another. The overlapping between adjacent base pairs creates base stacking interaction which further stabilizes the helical structure.
e. The backbones of two strands form two ridges on the surface of the helix. The two ridges: major groove and minor groove.
Shorter and fatter 12/ 0.38nm Longer and thinner 10/ 0.34nm Secondary structure of DNA 11/ 0.23nm dsDNA may have different conforma- tions under different conditions due to The structural flexibility. DNA conformation are involved in gene expression. dehydrated left-handed
dsDNA can be further twisted to form a supercoiled or superhelical structure due to its structural flexibility. 2.2 The native DNA is supercoiled and has a highly organized structure. Positive Twisted direction with respect to the helical direction supercoile Negative
Most prokaryotic DNA molecule are closed circular form. Negative supercoiled
Eukaryotic DNA molecules are lengthy and linear. Eukaryotic DNA need to be packed into nuclei in a highly organized form. Eukaryotic DNA becomes a condensed chromosome during the metaphase and becomes a form of chromatin in the rest phase of the cell cycle.
2.3 DNA can be replicated and transcribed. Function of DNA: the chemical basis of heredity, and the genetic information is organized in the form of genes. Replication: DNA carries the genetic information to offspring by making relatively error-free copies. Transcription: DNA serves as a template to direct the synthesis of RNA. Translation: RNA direct the synthesis of protein.
DNA base pair Prictice: Write the sequence .
The discovery of DNA double helix • Chargaff's Rule (A=T, G=C in DNA) • Franklin, Wilkins: X-ray DiffractionRefined Structure
Significance of DNA double helix semi-conservative model of DNA replication
