1.2.4 Nucleic Acids

Unit 1  The region of the enzyme that binds the substrate and contains the catalytic residues is known as the active site.

Cell signalling and ligand binding

Many proteins are involved in the process of cell signalling and signal transduction. Some proteins, such as insulin, are extracellular proteins that transmit a signal from the cell in which they were synthesized to other cells in distant tissues. Many receptors have a binding site exposed on the cell surface and an effector domain within the cell, which may have enzymatic activity or may undergo a conformational change detected by other proteins within the cell

 Antibodies are protein components of an adaptive immune system whose main function is to bind antigens, or foreign substances in the body, and target them for destruction.  Antibodies can be secreted into the extracellular environment or anchored in the membranes of specialized B cells known as plasma cells.  Whereas enzymes are limited in their binding affinity for their substrates by the necessity of conducting their reaction, antibodies have no such constraints. An antibody's binding affinity to its target is extraordinarily high.  Many ligand transport proteins bind particular small biomolecules and transport them to other locations in the body of a multicellular organism. These proteins must have a high binding affinity when their ligand is present in high concentrations, but must also release the ligand when it is present at low concentrations in the target tissues.  The ligand-binding protein is haemoglobin transports oxygen from the lungs to other organs and tissues in all vertebrates and has close homologs in every biological kingdom  Lectins are sugar-binding proteins which are highly specific for their sugar moieties. Lectins typically play a role in biological recognition phenomena involving cells and proteins Receptors and hormones are highly specific binding proteins.  Transmembrane proteins can also serve as ligand transport proteins that alter the permeability of the cell membrane to small molecules and ions. The membrane alone has a hydrophobic core through which polar or charged molecules cannot diffuse.  Membrane proteins contain internal channels that allow such molecules to enter and exit the cell.

Many ion channel proteins are specialized to select for only a particular ion; for example, potassium and sodium channels often discriminate for only one of the two ions

Structural proteins

Structural proteins confer stiffness and rigidity to fluid biological components. Most structural proteins are fibrous proteins; for example, collagen and elastin are critical components of connective tissue such as cartilage, and keratin is found in hard or filamentous structures such as hair, nails, feathers, hooves, and some animal shells. Some globular proteins can also play structural functions, for example, actin and tubulin are globular and soluble as monomers, but polymerize to form long, stiff fibres that make up the cytoskeleton, which allows the cell to maintain its shape and size.  Motor proteins such as myosin, kinesin, and dynein, which are capable of generating mechanical forces. These proteins are crucial for cellular motility of single celled organisms and the sperm of many multicellular organisms which reproduce sexually. They also generate the forces exerted by contracting muscles and play essential roles in intracellular transport.

1.2.4 Nucleic Acids

Nucleic acid, naturally occurring chemical compound that is capable of being broken down to yield phosphoric acid, sugars, and a mixture of organic bases (purines and pyrimidines). Nucleic acids are the main information-carrying molecules of the cell, and, by directing the process of protein synthesis, they determine the inherited characteristics of every living thing. The two main classes of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). DNA is the master blueprint for life and constitutes the genetic material in all free-living organisms and most viruses. RNA is the genetic material of certain viruses, but it is also found in all living cells, where it plays an important role in certain processes such as the making of proteins.

Unit 1 The first isolation of what we now refer to as DNA was accomplished by Johann Friedrich Miescher circa 1870. He reported finding a weakly acidic substance of unknown function in the nuclei of human white blood cells, and named this material "nuclein". A few years later, Miescher separated nuclein into protein and nucleic acid components. In the 1920's nucleic acids were found to be major components of chromosomes, small

gene-carrying bodies in the nuclei of complex cells. Elemental analysis of nucleic acids showed the presence of phosphorus, in addition to the usual C, H, N & O. Unlike proteins, nucleic acids contained no sulfur. Complete hydrolysis of chromosomal nucleic acids gave inorganic phosphate, 2-deoxyribose (a previously unknown sugar) and four different heterocyclic bases (shown in the following diagram). To reflect the unusual sugar component, chromosomal nucleic acids are called deoxyribonucleic acids, abbreviated DNA. Analogous nucleic acids in which the sugar component is ribose are termed ribonucleic acids, abbreviated RNA. The acidic character of the nucleic acids was attributed to the phosphoric acid moiety. Molecular composition

 Nucleic acids can vary in size, but are generally very large molecules. Indeed, DNA molecules are probably the largest individual molecules known.  nucleic acid molecules range in size from 21 nucleotides (small interfering RNA) to large chromosomes (human chromosome 1 is a single molecule that contains 247 million base pairs

Figure 10.17 A comparison of the two principal nucleic acids: RNA (left) and DNA (right), showing the helices and nucleobaseseach employs.

 In most cases, naturally occurring DNA molecules are double-stranded and RNA molecules are single-stranded. There are numerous exceptions, some viruses have genomes made of double-stranded RNA and other viruses have single-stranded DNA genomes, and, in some circumstances, nucleic acid structures with three or four strands can form.

 Nucleic acids are linear polymers (chains) of nucleotides. Each nucleotide consists of three components: a purine or pyrimidine nucleobases (sometimes termed nitrogenous base or simply base), a pentose sugar, and a phosphate group. The substructure consisting of a nucleobases plus sugar is termed a nucleoside.  Nucleic acid types differ in the structure of the sugar in their nucleotides - DNA contains 2'deoxyribose while RNA contains ribose (where the only difference is the presence of a hydroxyl group). Also, the nucleobases found in the two nucleic acid types are different: adenine, cytosine, and guanine are found in both RNA and DNA, while thymine occurs in DNA and uracil occurs in RNA.  The sugars and phosphates in nucleic acids are connected to each other in an alternating chain (sugar-phosphate backbone) through phosphodiester linkages. In conventional nomenclature, the carbons to which the phosphate groups attach are the 3'-end and the 5'end carbons of the sugar. This gives nucleic acids directionality, and the ends of nucleic acid molecules are referred to as 5'-end and 3'-end. The nucleobases are joined to the sugars via an N-glycosidic linkage involving a nucleobases ring nitrogen (N-1 for pyrimidines and N-9 for purines) and the 1' carbon of the pentose sugar ring.  Non-standard nucleosides are also found in both RNA and DNA and usually arise from modification of the standard nucleosides within the DNA molecule or the primary (initial) RNA

Figrue 10.18 Four nucleotide residues

Figure 10.19 The structure on the left - deoxyguanosine - depicts the base, sugar and phosphate moieties. In comparison, the structure on the right has an extra hydroxyl group on the 2' carbon of ribose, making it a ribonucleotide riboguanosine or just guanosine. In the right-hand figure, note also the 5' and 3' carbons on ribose (or deoxyribose) - understanding this concept and nomenclature is critical to understanding polarity of nucleic acids, as discussed below. The 5' carbon has an attached phosphate group, while the 3' carbon has a hydroxyl group.

transcript. Transfer RNA (tRNA) molecules contain a particularly large number of modified nucleosides.

Types of nucleic acids 1. Deoxyribonucleic acid (DNA)

Deoxyribonucleic acid is a nucleic acid containing the genetic instructions used in the development and functioning of all known living organisms (with the exception of RNA viruses). The DNA segments carrying this genetic information are called genes. Likewise, other DNA sequences have structural purposes, or are involved in regulating the use of this genetic information. Along with RNA and proteins, DNA is one of the three major macromolecules that are Figure 10.20 The process involving forming phosphodiester bonds between the 3' carbon of one nucleotide and the 5' carbon of another nucleotide. This leads to formation of the so-called "sugar-essential for all known forms of life. phosphate backbone", from which the bases project. A key feature  DNA consists of two long of all nucleic acids is that they have two distinctive ends: the 5' (5polymers of simple units prime) and 3' (3-prime) ends. This terminology refers to the 5' and 3' called nucleotides, with carbons on the sugar. For both DNA (shown above) and RNA, the 5' backbones made of sugars end bears a phosphate, and the 3' end a hydroxyl group. Another and phosphate groups joined by ester bonds. important concept in nucleic acid polymerases add nucleotides to incorporated base .Another way to structure is that DNA and RNA the 3' end of the previously put this is that nucleic acids are  These two strands run in synthesized in a 5' to 3' direction. opposite directions to each other and are therefore antiparallel. Attached to each sugar is one of four types of molecules called nucleobases (informally, bases).  It is the sequence of these four nucleobases along the backbone that encodes information. This information is Figure 10.21 The two strands of DNA are arranged antiparallel to one read using the another: viewed from left to right the "top" strand is aligned 5' to 3', while genetic code, which the "bottom" strand is aligned 3' to 5'. This is always the case for duplex specifies the nucleic acids. G-C base pairs have 3 hydrogen bonds, whereas A-T base sequence of the amino acids within pairs have 2 hydrogen bonds: one consequence of this disparity is that it takes more energy (e.g. a higher temperature) to disrupt GC-rich DNA than AT-rich DNA. proteins.  The code is read by copying stretches of DNA into the related nucleic acid RNA in a process called transcription. Within cell DNA is organized into long structures called chromosomes. During cell division these chromosomes are duplicated in the process of DNA replication, providing each cell its own complete set of chromosomes.  Eukaryotic organisms (animals, plants, fungi, and protists) store most of their DNA inside the cell nucleus and some of their DNA in organelles, such as mitochondria or chloroplasts.  Prokaryotes (bacteria and archea) store their DNA only in the cytoplasm. Within the chromosomes, chromatin proteins such as histones compact and organize DNA. These compact structures guide