Lecture 3 Molecular Biology ٣٢٥ Sabah Linjawi ١ What is nucleic acid? A nucleic acid is a macromolecule composed of chains of monomeric nucleotides These molecules carry genetic information or form structures within cells. The most common nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Nucleic acids are universal in living things, as they are found in all cells and viruses. Nucleic acids were first discovered by Friedrich Miescher in 1871. Molecular Biology ٣٢٥ Sabah Linjawi ٢ What is nucleic acid? The term "nucleic acid" is the generic name for a family of biopolymers, named for their role in the cell nucleus. The monomers from which nucleic acids are constructed are called nucleotides. Each nucleotide consists of three components: a nitrogenous heterocyclic base, which is either a purine or a pyrimidine; a pentose sugar; and a phosphate group. Molecular Biology ٣٢٥ Sabah Linjawi ٣ Building Blocks - Nucleotides Molecular Biology ٣٢٥ Sabah Linjawi A nucleotide is composed of three parts: pentose, base and phosphate group. In DNA or RNA, a pentose is associated with only one phosphate group but a cellular free nucleotide (such as ATP) may contain more than one phosphate group. If all phosphate groups are removed, a nucleotide becomes a nucleoside ٤ Pentose Molecular Biology ٣٢٥ Sabah Linjawi The chemical structure of pentose which contains five carbon atoms, labeled as C1' to C5'. The pentose is called ribose in RNA and deoxyribose in DNA because the DNA's pentose lacks an oxygen atom at C2'. Recalling that RNA stands for "ribonucleic acid", and DNA for "deoxyribonucleic acid". ٥ Bases Molecular Biology ٣٢٥ Sabah Linjawi There are five different bases, each is denoted by a single letter as given in the parenthesis: Adenine (A), Cytosine (C), Guanine (G), Thymine (T), and Uracil (U). Among them, A, C, G and T exist in DNA; A, C, G and U exist in RNA. Their chemical structures are shown in the following figure. A and G contain a pair of fused rings, classified as purines. C, T, and U contain only one ring, classified as pyrimidines. ٦ Cellular Nucleotides and Nucleosides Molecular Biology ٣٢٥ Sabah Linjawi In cells, a free nucleotide may contain one, two or three phosphate groups. The energy carrier ATP (adenosine triphosphate) has three phosphate groups ADP (adenosine diphosphate) has two AMP (adenosine monophosphate) has one. Their structures are shown in the following figure. ٧ The Nucleic Acid Chain Molecular Biology ٣٢٥ Sabah Linjawi In a nucleic acid chain, two nucleotides are linked by a phosphodiester bond, which may be formed by the condensation reaction similar to the formation of the peptide bond. In cells, such process has been found in the ligation between two nucleic acid fragments. However, the whole nucleic acid chain is usually synthesized by RNA polymerase or DNA polymerase. ٨ DNA Structure Molecular Biology ٣٢٥ Sabah Linjawi In a normal DNA molecule, adenine (A) is paired with thymine (T) guanine (G) is paired with cytosine (C). The uracil (U) of RNA can also pair with adenine (A) U differs from T by only a methyl group located on the other side of hydrogen bonding. A DNA molecule has two strands, held together by the hydrogen bonding between their bases adenine can form two hydrogen bonds with thymine cytosine can form three hydrogen bonds with guanine. ٩ DNA's B Form, A Form and Z Form Molecular Biology ٣٢٥ Sabah Linjawi In a DNA molecule, the two strands are not parallel, but intertwined with each other. Each strand looks like a helix. The two strands form a "double helix" structure, which was first discovered by James D. Watson and Francis Crick in 1953. This structure, also known as the B form, the helix makes a turn every 3.4 nm The distance between two neighboring base pairs is 0.34 nm. There are about 10 pairs per turn. The intertwined strands make two grooves of different widths The major groove and the minor groove, which may facilitate binding with specific proteins. ١٠ DNA's B Form, A Form and Z Form Molecular Biology ٣٢٥ Sabah Linjawi In a solution with higher salt concentrations or with alcohol added, the DNA structure may change to an A form, which is still righthanded, but every 2.3 nm makes a turn and there are 11 base pairs per turn. Another DNA structure is called the Z form, because its bases seem to zigzag. Z DNA is left-handed. One turn spans 4.6 nm, comprising 12 base pairs. ١١ RNA Structure and Function Most cellular RNA molecules are single stranded. They may form secondary structures such as stemloop and hairpin. Molecular Biology ٣٢٥ Sabah Linjawi ١٢ RNA Structure and Function The major role of RNA is to participate in protein synthesis, which requires three classes of RNA: messenger RNA (mRNA) transfer RNA (tRNA) ribosomal RNA (rRNA) Other classes of RNA include Ribozymes The RNA molecules with catalytic activity. Small RNA molecules RNA interference and other functions. Molecular Biology ٣٢٥ Sabah Linjawi ١٣ The mRNA-ribosome-tRNA complex formed during protein synthesis Molecular Biology ٣٢٥ Sabah Linjawi ١٤ References Wolfram Saenger, Principles of Nucleic Acid Structure, 1984, Springer-Verlag New York Inc. Keith Roberts, Martin Raff, Bruce Alberts, Peter Walter, Julian Lewis and Alexander Johnson, Molecular Biology of the Cell 4th Edition, Routledge, March, 2002, hardcover, 1616 pages, 7.6 pounds, ISBN 0-8153-3218-1 The Biochemistry of the Nucleic Acids - by Roger Lionel Poulter Adams, John T Knowler 708 pages Nucleic Acids in Chemistry and Biology - by G Michael Blackburn, ... - 503 pages The Double Helix: A Personal Account of the ... - by James D Watson, Gunther Siegmund Stent - 264 pages Links Interview with Aaron Klug, Nobel Laureate for structural elucidation of biologically important nucleic-acid protein complexes provided by the Vega Science Trust. Nucleic Acid Research Journal UC Berkeley video lecture on nucleic acids www.visionlearning.com/library/module_viewer.php?mid www.answers.com/topic/nucleic-acid Molecular Biology ٣٢٥ Sabah Linjawi ١٥
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