BCH 2011: Structure and function of cellular biomolecules

• Subject Convenor: Dr Janet Macaulay 
• Monash handbook
• 6 pts

This unit relates biomolecular structure with molecular function. Protein structure is explored and related to function in contexts such as cells and extracellular matrix. The folding of proteins into their active forms and the consequences of misfolding as a causative agent of disease is also explored. The mechanism of action of enzymes in medically important systems is examined. Students are introduced to the important role of membranes in cellular metabolism and the application of bioinformatics to proteins. Techniques used to study the structure and function of biomolecules and their application in the biotechnology industry are also introduced.

Lecturing Staff

Dr Janet Macaulay	A/Prof Martin Stone	Prof Steve Bottomley
Prof Rob Pike	Dr Peter Stanton

Organisation of the Unit

BCH2011 consists of 3 lectures per week and one 3 hour practical or small group session per week.

Practical/small teaching group classes are an integral part of BCH2011 and will reinforce concepts from lectures. The specific objectives of the practical/small group teaching program are to enable students to develop problem solving skills through the evaluation of biochemical data and to provide students with understanding and basic hands on experience of working in a laboratory. The activities include laboratory exercises, computer exercises, oral presentations and case studies.

Topics covered

Introduction: What is biochemistry? Why is structural biology/biochemistry important?

Role of water in cell biology: The role of water in biological systems. Physical properties of water. Introduction to pH, Buffers, both laboratory and physiological, and the effect of pH on molecular charge. Water movement. Water as a biological solvent - its role in biological reactions, hydrolysis and condensation reactions. Introduction to cell and tissue architecture, in relation to the dimensions of water molecules and biological macromolecules.

Structure and function relationships in proteins: Introduction to proteins. Amino acid structure, optical properties, different classes, ionisation states. Primary structure of proteins. Peptide bond. Peptides. Conservation of primary sequence. Disulfide bonding. Higher order structure of proteins, general forces involved, introduction to protein folding. Secondary structure. a-helix, b-sheet and b-turns. Hydrogen bonding in the maintenance of protein structure. Fibrous proteins. Globular proteins. Tertiary structure of proteins. Domain structure. Common structural patterns in proteins. Motifs. Quaternary structure. Influence of protein structure on function using myoglobin, haemoglobin and antibodies as examples.

Basics of protein synthesis. The genetic code. Stages of protein synthesis: activation of amino acids, initiation, elongation, termination and release, folding and post-translational processing.

Protein folding, misfolding: Introduction to the mechanisms of protein folding and misfolding. In these lectures we will discuss the mechanisms by which proteins fold to their correct three-dimensional structure, what happens when this process goes wrong and how this leads to disease.

Enzymes: Introduction to enzymes. What are they, what do they do and how do they do it? A comparison of the thermodynamics of catalysed and uncatalysed chemical reactions. Understanding how enzymes act as catalysts by lowering the activation energy of a reaction An examination of the different types of chemical reactions involved in catalysis and the role that co-factors play in catalysis. The kinetics of enzyme catalysed reactions. The importance of the Michaelis-Menten equation and methods of analysing kinetic data. Enzyme Inhibition. A comparison of the different modes of enzyme inhibition: competitive, uncompetitive and mixed modes. Enzyme regulation. An examination of the different modes of regulation including inhibition, allosteric enzymes and covalent modification. Chymotrypsin: an overview. An overview of the lecture series using the enzyme chymotrypsin as an illustration.

Techniques in biochemistry: General introduction to the purification of proteins. Precipitation of proteins. Dialysis. Chromatography. Gel filtration chromatography. Ion-exchange chromatography. Affinity chromatography. Analysis of proteins. Electrophoresis, PAGE, SDS-PAGE and SDS-PAGE. Amino acid analysis. Protein sequencing. Proteolytic mapping. HPLC. Mass spectrometry. Purification of example proteins, concepts and integration into a purification scheme.

Carbohydrates and glycoproteins: Basic chemistry of sugars. Orders of carbohydrate structure. The glycosidic bond. Structure of starch, glycogen, cellulose. Peptidoglycan in the cell wall. Antibiotic mechanisms. Glycoproteins. Functional glycoproteins, roles in biology. Structural glycoproteins, roles in extracellular matrix.

Lipid chemistry and biological membranes: Fatty acid structure and nomenclature. Structure of lipids. Steroid hormones, their structure and role in biology. Membrane structure in prokaryotes and eukaryotes. Membrane-bound proteins. Biological functions of membranes. Permeability. Transport across membranes. Lipids in Lipids in life, death and disease