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Course Guide 33132 Macromolecular Structure and Enzymology COURSE DATA Data Subject Código Name Cycle ECTS Credits Curso académico 33132 Macromolecular Structure and Enzymology Grade 7.5 2015 - 2016 Study (s) Degree Center 1109 - Grado de Bioquímica y Ciencias Biomédicas (2015) FACULTY OF BIOLOGICAL SCIENCES Subject-matter Degree 1109 - Grado de Bioquímica y Ciencias Biomédicas (2015) Subject-matter 8 - Bioquímica Acad. Period year 2 Character Obligatory SUMMARY "Structure of macromolecules and enzymology" is a compulsory course taught in the first quarter of the second year of the degree in Biochemistry and Biomedical Sciences with 7.5 ECTS credits. After completing this course is intended that students learn the biochemical principles of the structure of biological macromolecules and understand the main forces that stabilize them and allow specific interactions with other molecules. Also, students must understand the mechanisms of enzymatic reactions, kinetics and regulation. PREVIOUS KNOWLEDGE Relationship to other subjects of the same degree There are no specified enrollment restrictions with other subjects of the curriculum. Other requirements OUTCOMES 33132 Macromolecular Structure and Enzymology 1 Course Guide 33132 Macromolecular Structure and Enzymology 1101 - Grado de Bioquímica y Ciencias Biomédicas - Conocer los principios de la estructura de las macromoléculas biológicas DNA, RNA y Proteínas, y de las fuerzas que las estabilizan. - Relacionar la estructura de las macromoléculas con su función. - Conocer las interacciones que se establecen entre diferentes tipos de macromoléculas biológicas. - Conocer los mecanismos de las reacciones enzimáticas. Cinética enzimática. - Conocer los principios de activación e inhibición enzimática: efectos alostéricos y cooperativos. - Conocimiento y aplicación de los métodos experimentales y tecnología de enzimas. Análisis enzimático. - Aplicación de los conocimientos sobre estructura tridimensional de proteínas al estudio de la función de máquinas moleculares transductoras de energía. LEARNING OUTCOMES To understand the chemical and physical principles that determine the conformation of macromolecules. Knowing the molecular interactions that determine the properties and dynamics of macromolecules to form complexes with each other or with small ligands. Knowing the current models on the mechanisms of folding. To learn the main methodologies used for structural analysis of biological macromolecules. To understand databases and applications needed for the structural analysis of macromolecules. To understand the concept of enzyme and to know its general characteristics. Understanding the mechanisms of action for some model enzymes. Understanding the kinetic aspects and the mechanisms underlying its activity. Understanding the mechanisms of enzymatic regulation, mainly through reversible binding of ligands and the concepts of cooperativity and allosterism. Knowing the standard procedures used by scientists in the field of molecular biosciences to generate, transmit and disseminate scientific information Understanding the experimental approaches and their limitations and interpret scientific results. DESCRIPTION OF CONTENTS 1. Introduction Structural Biology: connections to other disciplines. Chemical composition of life. Biological polymers and macromolecular complexes. Weak interactions in aqueous media. Methods in Structural Biology 2. Protein Structure (I) Structure and classification of amino acids: hydrophobicity scales. The peptide bond. Structural levels of proteins. Determining the primary structure of proteins: peptide sequencing. Properties of the peptide bond. Conformational constraints of the peptides. Ramachandran plot. Secondary structure: α helix, β sheet and turns. Determination of secondary structure. Secondary structure prediction. 33132 Macromolecular Structure and Enzymology 2 Course Guide 33132 Macromolecular Structure and Enzymology 3. Protein Structure (II) Tertiary and quaternary structure of proteins. Structural classification of proteins. Fibrous proteins: alphakeratin, collagen and fibroin. Globular proteins. Supersecundary structures: motifs. Structural domains. Protein-proein interactions and cuaternary structure. Proteins α and β proteins. Structure determination by X-ray diffraction, nuclear magnetic resonance and electron microscopy. Tertiary structure prediction. 4. Protein Stability Main interactions protein stability. Concept of folding in vitro: hydrophobic effect. Native and denatured state. Thermodynamic stability of proteins. Protein folding. Transition states and intermediates (molten globule). Protein folding in the cell: molecular chaperones. Pathologies related to protein misfolding: Alzheimer's, Parkinson's and spongiform encephalopathies. 5. Macromolecular complexes Cylindrical assemblies: the proteasome and others. Nuclear pore complex. Protein filaments. Ribonucleoprtein complexes: the ribosome, the spliceosome and others. (1 hour) 6. Polysaccharides Monosaccharides and glycosidic bond. Structure of polysaccharides that function as store fuels: starch and glycogen. Polysaccharides with structural role: cellulose, chitin, glycosaminoglycans and peptidoglycans. Glycoconjugates. Molecular recognition and cell communication: the code of sugars and the role of lectins. 7. Biological membranes Amphipathic properties of the lipids. Lipid organization in aqueous solution: micelles, vesicles and bilayers. Composition of biological membranes. Membrane proteins: biosynthesis and folding. Structural examples: proton pumps, transporters and channels. 8. DNA Composition & Structure Nucleosides and nucleotides. Properties. Phosphodiester linkages. Determination of DNA secondary structure. Watson and Crick model of double helix. Detailed conformation of DNA and the sequence dependence. DNA structural variability. Other types of double helix: DNA B, DNA A DNA Z, H DNA, DNA G. Deformability and curvature. Triple helices: types. Denaturation and renaturation of the DNA. (5.5 hours) 9. High-order DNA Structure in genomes DNA in prokaryotes: supercoiling. Organization of the bacterial chromosome. Packaging of DNA in eukaryotic cells: chromatin. Histones. Nucleosomal structure of chromatin. Posttranslational modifications of histones. Higher levels of organization. (5 hours) 33132 Macromolecular Structure and Enzymology 3 Course Guide 33132 Macromolecular Structure and Enzymology 10. RNA Structure RNA types. Secondary and tertiary structure of RNAs. Secondary structure prediction. Riboswitches. Ribozymes.(1.5 hours) 11. Nucleic acids-protein interactions Examples. Protein-nucleic acid interactions. Binding to the major groove and minor groove. Examples. Methods of study. (2 hours). 13. Basic concepts Protein-ligand interactions: recognition and affinity. Association and dissociation constants. Cooperativity in ligand binding. Types of enzymes. The enzyme-substrate complex: the active site. Cofactors in enzyme activity. Classification and nomenclature of enzymes. Catalytic RNAs. 14. Enzyme kinetics Enzyme-substrate interaction. Energy and entropic effects. Energy profile of an enzymatic reaction: transition state and reaction intermediates. Effects of orientation and proximity. Mechanisms of enzymatic catalysis. Examples. 15. Enzyme kinetics: monosubstrate reactions The Michaelis-Menten equation. Meaning of the kinetic parameters: KM, Vmax and Kcat: efficiency and specificity. Determination of kinetic parameters. Effect of pH and temperature on reaction rate. Experimental methods for measuring enzyme activity. 16. Enzyme inhibition Types of inhibition. Reversible inhibition. Graphic representations. Significance of inhibition constants. Inhibition by competing substrates. Irreversible inhibitors. Applications of enzyme inhibition. 17. Enzyme kinetics: two or more substrates Bisubstrate reactions. Mechanisms ordered and random sequential and ping-pong mechanism. Rate equations. 18. Enzyme regulation Regulation of enzyme activity. Regulating the amount of enzyme. Isoenzymes. Covalent modification of enzymes: zymogens and enzymes interconvertible. Enzymatic cascades. Regulation by reversible binding of ligands: allosterism. Quantitative treatment of cooperativity: the Hill equation. Models of cooperativity and allosterism. 33132 Macromolecular Structure and Enzymology 4 Guía Docente 42681 Salud y Salud Pública 19. Macromolecular structure: bioinformatic tools Locally installed programs for analysis and modeling of structures. Introduction to the use of Swiss-Pdb Viwer and Swiss-Model Visit the main structural databases. Sequence Databases. Databases of 3D structures Libraries of structural motifs Libraries of structural families Libraries of ligands Tools Available on Web servers. Sequence alignment Secondary structure prediction Prediction of transmembrane segments Modeling by homology 20. Enzymology: practical lectures We will be use the computer program Grafit (RJ Leatherbarrow from Erithacus Software Ltd.) which allows theoretical simulations of chemical and enzyme kinetics, adjustment of experimental data and kinetic resolution of problems by iterative multiple kinetic equations included in the program. This program includes several examples of protein-ligand interaction with one or more independent and equivalent sites, adjustments to the equation of Adair, etc. It also allows adjustment of theoretical kinetic data and allosteric enzymes, representations of Eadie-Hofstee or Lineweaver-Burk plots for the study of inhibition or the determination of the contribution of the ionization state, or covalent modification of active site residues in the enzyme activity. WORKLOAD ACTIVITY Clases de teoría TOTAL Hours 24,00 24,00 % To be attended 100 TEACHING METHODOLOGY EVALUATION REFERENCES 42681 Salud y Salud Pública 5