Bio 160 4.1 - 4.3

How does the SECONDARY structure of RNA differ from DNA

*Like DNA, RNA 2ndary structure results from complementary base pairing [here, 2 H bonds form between A and U, while 3 H bonds form bt C and G] *In the vast majority of cases, the purine and pyrimidine bases in RNA undergo hydrogen bonding with complementary bases on the *same strand* , rather than forming hydrogen bonds with complementary bases on a different strand, as in DNA. *when bases on one part of an RNA strand fold over and align with bases on another part of the same strand, the two sugar-phosphate strands are antiparallel. In this orientation, hydrogen bonding between complementary bases results in a helical structure that resembles the double helix of DNA *Several types of 2ndary structure types of RNA are possible and form spontaneously [bases brought together by hydrophobic reactions and stabilized via hydrogen bonds and van der Walls]

Structure of DNA molecule

*antiparallel sugar-phosphate backbones forming sides of ladder *nitrogenous base pairs form rungs on ladder *Full helical turn every 3.4 nm (every 10 base pairs) *helical structure in order to make hydrogen bonding possible *Bases have polar groups involved w hydrogen bonding, but carbon-nitrogen ring is mostly nonpolar *hydrophobic interactions cause DNA to twist into helix to minimize contact between hydrophobic rings and water molecules *Paired strands stabilized by van der Waals interactions between tightly packed bases *Negatively charged phosphate groups facing molecule's exterior make DNA hydrophilic overall and thus aqueous *the outside of the helical DNA molecule forms two types of grooves: The wider of the two is known as the major groove, and the narrower one is known as the minor groove. This groove asymmetry is vital for granting access to proteins that bind to particular base sequences in DNA

Why can't DNA catalyze replication reactions itself? (i.e. self-replicate)

*relatively stable and unreactive structure makes molecule poor at catalysis *Thus, because there is no evidence supporting the idea that DNA can self-replicate, it is unlikely that they were the molecules present in the first forms of life -- rather, we think it was RNA

How does tertiary structure of RNA differ from DNA

*variety of tertiary structures form when secondary structures fold to form complex shapes *RNA molecules are much more diverse in size, shape, and reactivity than DNA molecules.

Tertiary structure of DNA

1. Supercoils: When DNA becomes wound too tightly or loosely with respect to the number of base pairs per helical turn, it can twist on itself to form compact, three-dimensional structures called supercoils 2. DNA often forms highly organized tertiary structures by *wrapping around certain proteins.* These DNA-protein complexes compact the DNA into discrete, movable units during cell division, and they also contribute to DNA's ability to store and transmit information

How did Watson and Crick's model explain the basis for Chargaff's rules and the results of Franklin and Wilkins' x-ray crystallography?

1. They arranged two strands of DNA side by side with the sugar-phosphate backbones on the outside and the bases on the inside. If the bases extending from each backbone are to fit within the interior of a 2.0-nm-wide structure, then they have to form purine-pyrimidine pairs 2. Purine-pyrimidine pairing allows hydrogen bonding to form only between certain bases (said to be complementary). For example, adenine will form two hydrogen bonds with thymine, and guanine will form three hydrogen bonds with cytosine {The third hydrogen bond in G-C pairs makes them slightly stronger than A-T pairs.} 3. The patterns of hydrogen bonding could form only if the bases on opposite strands were flipped 180 degrees relative to one another. For this to happen, the two parallel strands of DNA must be oriented in opposite directions—meaning that one strand runs in the 5´ → 3´ direction while the other strand runs 3´ → 5´ {ANTIPARALLEL ORIENTATION} 4. antiparallel strands were predicted to be twisted together to form a double helix.

Steps involved in copying of DNA

1. Two strands of DNA can be separated by breaking hydrogen bonds that hold them together using either hear or enzyme-catalyzed reactions 2. Free deoxyribonucleotides form hydrogen bonds w complementary bases on the original strand of DNA (template strand). As this happens, sugar-phosphate groups form phosphodiester linkages to create a new (complementary) strand [ 5∙ S 3∙ directionality of the complementary strand is the opposite to that of the template strand.] 3. Complementary base pairing allows each strand of DNA double helix to be copied exactly, producing two identical daughter molecules

early data which provided clues to DNA's secondary structure

1. Watson and Crick knew that DNA had a sugar-phosphate backbone since early research showed that DNA formed from the polymerization of phosphodiester linkages 2. Erwin Chargaff found that (1) a molecule of DNA had equal numbers of pyrimidines and purines, and (2) DNA molecules have equal numbers of C and G, as well as equal numbers of A and T 3. X-ray crystallography by Franklin and Wilkins calculated distances between groups of atoms in the molecule; scattering patterns of radiation revealed three repeating distances: .34 nm, 2.0 nm, and 3.4 nm [researchers inferred that DNA had repeating, helical structure]

The first living molecule would have needed to perform two functions:

1. carry information 2. catalyze reactions that promoted its own replication. At first glance, these two functions appear to conflict. Information storage requires regularity and stability; catalysis requires variation in chemical composition and flexibility in shape

Two structural groups of nitrogenous bases

1. pyrimidines: single-ringed nitrogenous bases (cytosine, uracil, thymine) found in nucleotides (6 atoms) 2. purines: double-ringed nitrogenous bases (guanine, adenine) found in nucleotides (9 atoms - guaNINE and adeNINE)

Direction of nucleotide addition

5' to 3' (only added at the 3' end of a growing molecule)

nucleic acid

A macromolecule (polymer) composed of nucleotide monomers. Generally used by cells to store or transmit hereditary information. Includes ribonucleic acid and deoxyribonucleic acid

nucleotides

A molecule consisting of a five-carbon sugar (ribose or deoxyribose), one or more phosphate groups, and one of several nitrogen-containing bases. Equivalent to a nucleoside plus one or more phosphate groups phosphate group is bonded to the sugar molecules, which is bonded to the nitrogeneous base the base is attached to the 1∙ carbon on sugar and the phosphate group is attached to the 5∙ carbon.

deoxyribonucleotide

A nucleotide consisting of a deoxyribose sugar, one or more phosphates, and one of four nitrogen-containing bases: adenine, guanine, cytosine, or thymine monomer for deoxyribonucelic acid

ribonucleotide

A nucleotide consisting of a ribose sugar, one or more phosphates, and one of four nitrogen-containing bases: adenine, guanine, cytosine, or uracil monomer for ribonucleic acid

hairpin

A secondary structure in RNA consisting of a loop of single-stranded RNA at the end of a double helix that is formed by complementary base pairing within the same strand

x-ray crystallography

A technique for determining the three-dimensional structure of large molecules, including proteins and nucleic acids, by analyzing the diffraction patterns produced by X-rays beamed at crystals of the molecule.

Could Nucleic Acids Have Formed in the Absence of Cellular Enzymes?

Based on the results of many experiments, there is a strong consensus that if activated ribonucleotides and deoxyribonucleotides were able to form during chemical evolution, they could have polymerized into DNA and RNA without protein-based catalysts

phosphodiester linkage

Chemical linkage between adjacent nucleotide residues in DNA and RNA. Forms when the phosphate group of one nucleotide condenses with the hydroxyl group on the sugar of another nucleotide. Also known as phosphodiester bond chain of phosphodiester linkages in a nucleic acid acts as a backbone

DNA Functions as an Information-Containing Molecule

DNA stores and transmits biological information in the form of nucleotide sequences in nucleic acids DNA's primary structure serves as a template for the synthesis of a complementary strand, meaning that DNA contains the information required for a copy of itself to be made

antiparallel

Describes the opposite orientation of nucleic acid strands that are hydrogen-bonded to one another, with one strand running in the 5∙ S 3∙ direction and the other in the 3∙ S 5∙ direction.

DNA and RNA strands are directional

In a strand of DNA or RNA, the sugar-phosphate backbone of a nucleic acid is directional: one end has an unlinked 5∙ phosphate while the other end has an unlinked 3∙ hydroxyl—meaning the groups are not bonded to another nucleotide. The primary structure of a stretch of DNA or RNA is written as the sequence of bases by their single-letter abbreviations in the 5´ → 3´ direction. (This system is logical because in cells, RNA and DNA are always synthesized in this direction. Nucleotides are added only at the 3∙ end of the growing molecule.)

Could chemical evolution result in the production of nucleotides?

Miller-like laboratory simulations have shown that nitrogenous bases and many different types of sugars, including ribose, can be synthesized readily under conditions that mimic the prebiotic soup. Recent work has focused on the conditions that exist in deep-sea hydrothermal vent systems Results: In a pool of a diverse array of sugars, minerals preferentially bound to RIBOSE Implications: A high concentration of ribose would be present in the same deep-sea vent environment where the evolution of life is thought to have taken place...so nucleotide synthesis could have occurred!

nucleoside triphosphate

Molecule consisting of a nitrogenous base, a pentose sugar, and three phosphate groups, e.g., adenosine triphosphate (ATP)]

Can DNA catalyze the reactions needed to self-replicate?

No. the molecule is copied through a complicated series of reactions that are catalyzed by enzymes

Drawing nucleotides

Nucleotides are often drawn using a circle for the phosphate group, a pentagon with a tail for the sugar, and a hexagon for the base. Lines connecting the shapes represent covalent bonds.

the DNA double helix is a stable structure

The DNA double helix is highly structured. It is regular, symmetric, and held together by phosphodiester linkages, hydrogen bonding, and hydrophobic interactions. In addition, the double helix has few functional groups exposed that can participate in chemical reactions, making the molecule particularly stable and resistant to degradation. Orderliness and stability make DNA good for storing information, but bad at catalysis.

complementary base pairing

The association between specific nitrogenous bases of nucleic acids stabilized by hydrogen bonding. Adenine pairs with thymine (in DNA) or uracil (in RNA), and guanine pairs with cytosine. (see also Watson-Crick pairing)

Why does polymerization require an energy source?

The joining of nucleotides drastically decreases entropy and is thus not spontaneous, therefore, an input of energy is needed in order to tip the balance in favor of polymerization

How is energy input into the polymerization process forming nucleic acids?

The potential energy of the nucleotide monomers is first raised by reactions that add two phosphate groups to the ribonucleotides or deoxyribonucleotides, creating nucleoside triphosphates. These phosphate groups raise the potential energy of a molecule since they are negatively charged and like charges repel. So, linking 2+ phosphate groups together generates a covalent bond that carries a large amount of energy due to strong repulsion forces. The energy is released when the phosphates form new, more stable bonds with other atoms (i.e. through hydrolysis) When activated nucleotides polymerize, the energy released from the condensation reaction compensates for the decrease in entropy, making the reaction spontaneous.

double helix

The secondary structure of DNA, consisting of two antiparallel DNA strands wound around each other

RNA's versatility

The structural flexibility of RNA molecules allows them to perform many different tasks.

Drawing DNA molecules

The sugar-phosphate backbone can be simplified to a single line with an arrowhead to identify the 3∙ end. Base pairing is drawn as short lines and, if the sequence is part of the model, nucleotides are represented by letters.

How does the PRIMARY structure of RNA differ from DNA

They both have 4 nitrogenous bases extending from a sugar-phosphate backbone, but 1) the sugar in the sugar-phosphate backbone is ribose - not deoxyribose 2) The pyrimidine base thymine does not exist in RNA, instead, it uses Uracil *Ribose has an extra -OH group, which makes RNA less stable than DNA since the hydroxyl group can attack the phosphate linkage between nucleotides, which would generate a break in the sugar-phosphate backbone. This instability can support catalytic activities`

2.0 nm and .34 nm

Watson and Crick decided that these numbers represented the width of the molecule and distance between the bases stacked in the helix, respectively.

Polymerization reactions that form nucleotides into nucleic acids

are catalyzed by enzymes

activated nucleotides

nucleoside triphosphates used in nucleic acid polymerization

How do nucleotides polymerize to form nucleic acids?

nucleotides polymerize via *condensation reactions* between the hydroxyl on the sugar component of one nucleotide and the phosphate group of another nucleotide. The reaction forms a new covalent bond—called a phosphodiester linkage, or a phosphodiester bond—between the nucleotides, and a molecule of water is released. phosphodiester linkage connects the 3∙ carbon of one nucleotide and the 5∙ carbon of another nucleotide.

describe the difference between deoxyribonucleotides and ribonucleotides

ribonucleotides -are the monomers for RNA -has ribose sugar -has OH group bonded to the 2∙ carbon -use Uracil as one of its nitrogenous bases deoxyribonucleotides -monomers for DNA -deoxyribose sugar -has only H bonded to 2∙ carbon -use Thymine as one of its nitrogenous bases

RNA can function as a catalytic molecule

ribozymes, or RNA enzymes, catalyze reactions similar to protein enzymes ribozyme catalyzes both the hydrolysis and the condensation of phosphodiester linkages in RNA raised the possibility that an RNA molecule could polymerize a copy of itself. Such a molecule could qualify as the first living entity. The three-dimensional nature of ribozymes is vital to their catalytic activity. (Folding brings wide-spread nucleotides together at the active site)

nucleoside

sugar + base

DNA molecule

sugar-phosphate backbone breated by phosphodiester linkages and sequence of any four nitrogen bases extending from it