Tuesday, 13 October 2020

Structure of Nucleic acids DNA & RNA

Nucleic acids DNA and RNA structure


  Nucleic acids are polymers of nucleotides.They were first reported from nucleus of pus cells by Friederich Miescher in 1868 as nuclein.

Basic chemistry of nucleic :
acids Nucleotides are the building blocks of nucleic acids, which are linked by phosphodiester bonds.  Nucleotides are made of nitrogen bases, pentose sugar and phosphoric acid,


a). Nitrogen bases
   The bases of nucleic acids are ring structures of carbon that contain nitrogen atom within.  There are two types of bases found in nucleic acids. 
    l).  Purines
   ll).  Pyrimidine

Purine :
  Purines are fused ring structures having one six member and another five member ring.  Depending on the type and position of side chain attached, they are of two different types;  adenine and guanine. 

Pyrimidines :
Pyrimidines consist of a single six member ring structure.  Three types of pyrimidines are found: uracil, cytosine and thymine.  They differ in the type and position of side chains attached to the ring or these, DNA contains thymine and cytosine, while RNA contains uracil cytosine. there is a difference between thymine and uracil is 2' carbon methyl group which present on thymine insted of hydrogen in uracil.


b). Pentose Sugar


The pentose sugar found in nucleic acid can be either ribose or deoxyribose. Ribose is associated with RNA while deaxyribose is found in DNA.
Phosphoric acid Nucleotides contain a phosphate group attached to pentose.


c). Nucleoside : When a nitrogen base is attached to a pentose sugar, the compound is called nucleoside. The nitrogen base attaches to the pentose sugar at its first carbon by N- glycosidic bond.

There are eight types of nucleosides depending on the type of nitrogen base and pentose sugar associated. Deoxynucleosides: Deoxyadenosine, Deoxyguanosine, Deoxycytidine, Deoxythyimidine Ribonucleosides: Adenosine, Guanosine, Cytidine, Thmidine


d). Nucleotide : When a phosphate group is bound to a nucleoside by phospoester bond, the complex is called nucleotide. The phosphate group is bound to nucleoside at fifth carbon of pentose sugar.

Based on the type of sugar and nitrogen base involved, there are eight types of nucleotides, which could be classifled into two major categories: Deoxyribonucleotides and Ribonucleotides.
  Depending on the number of phosphate groups present, the nucleotides can be designated as nucleoside monophosphate (NMP), nucleoside diphosphate (NDP). nucleoside triphosphate (NTP). The nucleotides containing deoxyribose sugar are designated dNTP, dNDP, and dNMP. In nucleotides, the last two phosphate groups are linked by high energy phosphoester bonds.

Polynucleotide :
The nucleotides can be held together by phosphodiester linkage to form a polymer.The bond forms between the -OH group present on the 3rd carbon of pentose of one nucleotide and PO4, group present on fifth carbon of sugar of the other nucleotide. Hundreds to millions of nucleotides can be polymerized in a nucleic acid. Each polymer possesses two ends: 3' - OH end and 5' - PO4, end having a free OH group and phosphate group respectively.


e). Types of nucleic acids:
  There are two types of nucleic acids: DNA and RNA. DNA exists as the genetic material in all living organisms, except in certain viruses. RNA plays vital role in protein synthesis, by carrying information from DNA to cytoplasm. Also, in certain viruses,


DNA

Deoxyribonucleic acid is a polymer of deoxyribonucleotides. It is the genetic material, found in all living organisms, except certain viruses. It carries the blue print of the characters shown by organisms.
  The DNA possesses a characteristic base sequence that forms the basis of genetic information and diversity. The sequence of bases, responsible for the expression of a particular character is known as gene.

Chemistry of DNA :
  DNA contains four types of deoxyribonucleotides having adenine, cytosine, guanine and thymine. Studies of Chargaff on DNA chemistry have shown that 

a).  All DNA possess purine and
     pyrimidine in equal proportion  
     (1 : 1 ratio)
b). All DNA have A=T and G=C. c). DNA form different sources 
      have a characteristic AT/GC  
      ratio and AT GC.

Structure of DNA :
Watson and Crick (1953) worked out a three dimensional structure of DNA based on X-ray diffraction photographs. They proposed a double stranded helical structure of DNA.

Salient features of Watson and Crick model of DNA double helix

1).  The DNA molecule consists of two strands of polynucleotides held together by hydrogen bonds between them. 2).  The two strands run anti parallel at a distance of 20A. One strand runs from 5 → 3' direction, while the other strand runs from 3'→ 5' direction.
3).  The two strands are helically coiled around an imaginary axis, forming right handed helix.
4).  Each turn of the double helix is 34 A° long and accommodates ten base pairs. The distance between two successive base pairs in the DNA is 3.4 A°.
5).  The bases are arranged almost perpendicular to the central axis of the double helix. In the structure, the hydrophilic sugar phosphate groups form outer back bone. The hydrophobic nitrogen bases remain inside the structure.
6).  The double helix shows presence of two grooves: a major or deep groove and a minor or shallow groove.
7).  In the double helix, pairing takes place between adenine and thymine as well as guanine and cytosine.

Adenine pair with thymine by forming two hydrogen bonds between  them. Guanine and cytosine pair by forming three hydrogen bonds between them.

Acceptability of Watson and Cricks structure of DNA

1). Pairing is possible between purine and pyrimidine bases only to allow and accommodate hydrogen bonds between them. Two purines, being larger molecules cannot be accommodated in the double helix having diameter of 20 A°. Two pyrimidines, being smaller molecules, also cannot form hydrogen bonds, leaving a too large space between them. This explains, why in DNA purine - pyrimidine ratio is 1, according to Charggaff's rule.

2.) Structural complimentarily exists between adenine and thymine as well as guanine and cytosine allowing hydrogen bonds between them and pair. This also explains, why in DNA, A=T and G=C, according to Chargaff's rule.

3). The structure docs not put any restrictions on the sequence of bases in DNA. Therefore, in DNA it is not cssential to have AT = GC. Its ratio can be different in different DNA, as observed by Chargaff.
Further, this also explains, how a sequence of four bases can decide for diversity in characters.

4). The structure can also allow understanding how DNA replicates. Crick proposed that at the time of replication, the two strands of DNA could separate, and act as template, allowing complementary strand to be synthesized. As a result, two daughter molecules of DNA could be formed having identical sequence, as found in mother DNA molecule. This pattern of replication is called semi conservative replication.

RNA

  RNA is a polymer of ribonucleotides held together by phosphodiester bonds. The nucleotides of RNA contain adenine, guanine, cytosine and uracil.
A large variety of RNA forms are found in cell, having molecular weight ranging from just 25000 to several millions. Most RNAS are single stranded. But many times, folded RNA molecules having secondary and tertiary structures are also observed.

Types of RNA :
  There are threc major types of RNA.

1. Transfer RNA or tRNA
2. Messenger RNA or mRNA
3. Ribosomal RNA or rRNA

tRNA
These are the smallest types of RNA having 70 to 80 bases in the structure. They are named so because they transfer amino acid from cytoplasm to ribosome for protein synthesis. They comprise about 10- 20% of total RNAs in cell. There are at least 20 types tRNAs in the cell, one each for a specific amino acid. tRNAS are unique in composition as they contain abnormal or modified bases such as pseudo uridine, inosine and methyl nucleosides.
   

 tRNA have a secondary structure, and are clover leaf in shape having


1). Aminoacyl arm at which amino acid can bind.
2). D loop arm and loop, that contain abnormal base, dihydroxy uridine and possess binding site for amino acid activating enzyme that allows tRNA to carry amino acid.
3). Anticodon arm and loop, that contain anticodon, which has complementarily with codon and allow proper codon anticodon pairing between tRNA and mRNA during protein synthesis. 

4). T loop arm that contain abhormal base, pseudouracil in the sequence TΨC. It allows proper positioning of tRNA on ribosome during protein synthesis. 

5). Optional or pseudo arm having variable length with C. 3 to 21 bases.

mRNA
  The RNA that carries message for the type of protein to be synthesized is called mRNA or messenger RNA. The length of mRNA depends on the size of protein it codes for.
  mRNA possess a codon sequence, which decides for sequence of amino acids to be polymerized during protein synthesis. Codon is a sequence of three bases, triplet, specific for cach amino acid.

In addition, mRNA also possesses signal codons.
1. Initiation codon which provide signal for initiation for protein synthesis and
2. termination codon, which provide signal for termination of protein synthesis.
  Initiation codon is always first AUG codon on 5' end of mRNA. Termination codon is a nonsense codon, that does not code for any amino acid. They are UAA, UAG and UGA.

rRNA
  rRNAs associated with structure of ribosome are called ribosomal RNA or rRNA. They are structural RNAs, associated with ribosomal proteins. Different species of rRNA are found in cell as shown below in table 

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