Essentials of Chemical Biology

Structure and Dynamics of Biological Macromolecules

Andrew D. Miller, Julian A. Tanner

• Editore: Wiley
• Anno: 2013
• ISBN:
  9781118687833
• Edizione: 1
• Argomento: Scienze biologiche
• Categoria: Biochimica

"This excellent work fills the need for an upper-level graduate course resource that examines the latest biochemical, biophysical, and molecular biological methods for analyzing the structures and physical properties of biomolecules… This reviewer showed [the book] to several of his senior graduate students, and they unanimously gave the book rave reviews. Summing Up: Highly recommended..."
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Chemical biology is a rapidly developing branch of chemistry, which sets out to understand the way biology works at the molecular level. Fundamental to chemical biology is a detailed understanding of the syntheses, structures and behaviours of biological macromolecules and macromolecular lipid assemblies that together represent the primary constituents of all cells and all organisms. The subject area of chemical biology bridges many different disciplines and is fast becoming an integral part of academic and commercial research.

This textbook is designed specifically as a key teaching resource for chemical biology that is intended to build on foundations lain down by introductory physical and organic chemistry courses. This book is an invaluable text for advanced undergraduates taking biological, bioorganic, organic and structural chemistry courses. It is also of interest to biochemists and molecular biologists, as well as professionals within the medical and pharmaceutical industry.

Key Features:

• A comprehensive introduction to this dynamic area of chemistry, which will equip chemists for the task of understanding and studying the underlying principles behind the functioning of biological macro molecules, macromolecular lipid assemblies and cells.
• Covers many basic concepts and ideas associated with the study of the interface between chemistry and biology.
• Includes pedagogical features such as: key examples, glossary of equations, further reading and links to websites.
• Clearly written and richly illustrated in full colour.

1

The Structures of Biological Macromolecules and Lipid Assemblies

1.1 General introduction

All living organisms are comprised of cells that may vary considerably in terms of size, shape and appearance; in complex multicellular organisms, many cells are organised into diverse, functional organs to perform a collective function (Figure 1.1). In spite of their wide morphological diversity, all cells of all living organisms, wherever they are located, are comprised of proteins, carbohydrates, nucleic acids and lipid assemblies. These together give a cell form and function. To know and understand the chemistry of these biological macromolecules is to comprehend the basic infrastructure not only of a cell but also of living organisms. In functional terms, macromolecular lipid assemblies provide for compartmentalisation in the form of membrane barriers, which not only define the ‘outer limits’ of each cell but also divide up the intracellular environment into different organelles or functional zones (Figure 1.2). Membrane barriers are fluidic and lack rigidity, so proteins provide a supporting and scaffolding function not only in the main fluid bulk of the cell, known as the cytosol, but also within organelles. Within the nucleus, proteins also provide a nucleic acid packaging function in order to restrain and constrain spectacular quantities of nucleic acids within the nuclear volume. Everywhere in any cell, proteins also perform other individualised functions in outer membranes (as pores or receptors for example), in organelle membranes (as selective transporters, redox acceptors or energy transducers), in the cytosol or organelle volumes (as enzyme catalysts, molecular chaperones or ‘communication and control’ centres) and in the nucleus (as regulators and transcribers of the genetic code). The extraordinary variety of protein functions and the ‘workhorse’-like nature of proteins in biology has made them endlessly fascinating to biochemists and now to chemical biologists alike.

Figure 1.1 Organs and Cells. (a) cross section of mammalian brain showing the complex surface folds. There are an incalculable number of cells that make up the mammalian brain; (b) cross section of mammalian eye ball in which the lens is made of proteins controlled in function by peripheral muscles. There is an enormous morphological and functional diversity between cells required for muscle control, light reception, and signal transduction along the optic nerve; (c) cross section of mammalian neurological tissue illustrating the neuron cell bodies with complex axonal/dendritic processes surrounded by support cells all of a wide range of size, shape, structure and function; (d) cross section of mammalian heart tissue showing clusters of muscle fibres (single cell myocytes) that make up the heart wall. Myocytes are multinucleate with a very different shape, composition and function to neurological cells (all illustrations from Philip Harris Ltd, Weston Super Mare, UK).

Nucleic acids are found in two main classes, namely deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). DNA is largely restricted to the nucleus and harbours genetic information that defines the composition and structure of cells and even the multicellular organisation of complex organisms, reaching even beyond this to influence organism behaviour as well. DNA molecules are partly segmented into genes that contain coding information for protein structures, but also into many other delineations associated with control over gene use. In fact, the level and sophistication of this control may well be the primary determinant of complexity in multicellular organisms: the more extensive and sophisticated the level of control, the more sophisticated and complex the multicellular organism. By contrast, RNA’s most important role is in shuttling information from the nucleus to the cytosol. The primary function of RNA equates to the processing of genetic information from the DNA storage form into actual protein structures. RNA makes possible the central dogma of biology, that genes code for proteins. Finally, carbohydrates, if not stored in complex forms for primary metabolism, are known to decorate some intracellular proteins and attach to outer membrane proteins, forming a glycocalyx covering the surface of many cells, essential for communication between cells. In the plant and insect kingdoms, gigantic carbohydrate assemblies also provide the exoskeleton framework to which cells are attached, giving form as well as function to plants and insects alike.

Figure 1.2 General structure of a cell showing the main compartments (organelles) into which the interior is partitioned. All cells of all organisms are constructed from the main biological macromolecules proteins, carbohydrates, and nucleic acids; together with macromolecular lipid structures that comprise the membranes. (illustration from Philip Harris Ltd, Weston Super Mare, UK).

In all cases, proteins, carbohydrates and nucleic acids are polymers built from standard basis sets of molecular building blocks. In a similar way, lipid assemblies are built from a standard basis set of lipid building blocks associated through non-covalent bonds. What all biological macromolecules and macromolecular assemblies have in common is that they then adopt defined three dimensional structures that are the key to their functions (dynamics, binding and reactivity). Remarkably, these three dimensional structures are not only central to function but they are the result of weak, non-covalent forces of association acting together with stereoelectronic properties inherent within each class of polymer or macromolecular assembly. Without structure, function is hard to understand, although structure does not necessarily predict function. Therefore, the chemical biology reader needs to have a feel for the structures of proteins, carbohydrates, nucleic acids and lipid assemblies before embarking on any other part of this fascinating subject. Accordingly, the principles of structure are our main topic for Chapter 1, concluding with some explanation about those critical weak non-covalent forces of association that are all so important in shaping and maintaining these structures.

1.2 Protein structure

1.2.1 Primary structure

Proteins are polymers formed primarily from the linear combination of 20 naturally occurring L-α-amino acids, which are illustrated (Table 1.1) (Figure 1.3). Almost all known protein structures are constructed from this fundamental set of 20 α-amino-acid building blocks. These building blocks fall into two main classes, hydrophobic and hydrophilic, according to the nature of their side-chains (Table 1.1). Protein architecture is intimately dependent upon having two such opposite sets of α-amino-acid building blocks to call upon. Individual α-amino-acid building blocks are joined together by a peptide link (Figure 1.4). When a small number (2–20) of amino acids are joined together by peptide links to form an unbranched chain, then the result is known as an oligopeptide (Figure 1.5). However, peptide links can join together anything from 20 to 2000 amino-acid residues in length to form substantial unbranched polymeric chains of L-α-amino acids. These are known as polypeptides. Within each polypeptide chain, the repeat unit (–N–C_α–C(O)–)n, neglecting the α-amino-acid side-chains, is known as the main c...