69162 - Chemical Structures Of Biological System

Learning outcomes

At the end of the course the student will acquire the theoretical basis for understanding the relationship between the molecular structure of enzymes and the biochemical reactions that they catalyze, with specific focus on the bioinorganic aspects of metalloenzymes and metalloproteins. He will be able to acquire information on protein sequence and structure and of interpreting them, together with spectroscopic data, to evaluate the structural and chemical changes occurring to molecules within the food.

Course contents

• Primary structure of proteins and physicochemical properties of their amino acid constituents
• Secondary structure and Ramachandran plot
• Tertiary and quaternary structure
• Folding thermodynamics, Levinthal's paradox
• Conformational flexibility and stability
• Cofactors, prosthetic groups, apo and holo-proteins
• Sequence homology and conservation of structure and biological function
• Description and use of sequence databases (ncbi, uniprot) and structure databases (Protein Data Bank)
• Description and use of bioinformatics programs for validation of protein structures (molmol/Pymol and CLUSTALX)
• NMR parameters and information on the chemical nature of biological systems
• NMR spectroscopy for the elucidation of the structures
• X-ray crystallography and cryo-electron microscopy
• Metal ions abundance in nature and in biological fluids
• Uptake of metal ions in the cells
• Transferrin, siderophores and Chaperones
• Enterobactin and competitive inhibition of ferric-MECAM
• Principles of chemical kinetics and Arrhenius law
• Michaelis-Menten kinetics and saturation
• Hints on Hard-Soft theory
• Dissociation constants and affinity
• Defining the catalytic site and mechanisms of enzymatic reactions
• Metal ions and effect of coordination on the acidic constant of water
• Role of metal ions in hydrolytic enzymes
• Mechanism of action of carboxy peptidase and carbonic anhydrase
  
• Transduction of the chemical signal into mechanical energy: contractile proteins
• Structural differences between hemoglobin and myoglobin and their implications in their different physiological function
• Electronic state of iron ions in the high and low spin
• NMR of myoglobin and adducts with cyanide
• Paramagnetic effect on the chemical shift of NMR signals
• Nuclear relaxation of the water protons: interaction with paramagnetic ions
• Water redox properties: oxygen and H+ ion reduction potentials 
• Role of the metal ion (Fe or Cu) and optimal coordination geometries in electronic transport
• Role of the geometry of the ligands on E0 of plastocyanin and azurin
• Redox potential of the proteins and pathways of electron transfer
• Frank-Condon effect and Marcus theory
• Catalytic mechanism of copper-zinc superoxide dismutase

Readings/Bibliography

• Lecture notes
• Scientific papers on international peer-reviewed journals
• Brändén, C., Tooze, J. (1999). Introduction to protein structure. United Kingdom: Garland Pub. ISBN: 9780815323051
• Bioinorganic Chemistry - I. Bertini, H.B. Gray, S.J. Lippard, J.S. Valentine (Eds.) -University Science Books, Mill Valley, CA, U.S.A., ISBN: 0935702571

Newer edition:

• Bertini, I., Gray, H. B., Stiefel, E. I., Valentine, J. S. (2007). Biological Inorganic Chemistry: Structure and Reactivity. United Kingdom: University Science Books. ISBN: 9781938787966
• Hore, P. J. (1995). Nuclear Magnetic Resonance (Oxford Chemistry Primers). United Kingdom: Oxford University Press. ISBN: 0198556829
• Rhodes, G. (2006). Crystallography Made Crystal Clear: A Guide for Users of Macromolecular Models. Netherlands: Elsevier Science. ISBN: 9780080455549

Teaching methods

The teaching consists of 4 ECTS. Each ECTS includes 6 hours of lectures and 4 hours of practical work in class. The practical work is carried out in the Computer Laboratory at the Campus of Cesena (Villa Almerici) with 20 PC workstations with access to the network. Students will follow the operations conducted by the teacher through the overhead screen projection. The objective of the practical exercises is twofold:

- To make the student familiar with the bioinformatic tools for the analysis of structural data

- To develop the student's ability to independently develop hypotheses on the relationships between structure and function of biological molecules

Assessment methods

The examination at the end of the course aims to assess the achievement of the following learning objectives:

- Using the information provided in class to describe the structural and functional characteristics of macromolecules

- Describing, with properties of language and scientific rigor, the mechanisms of function of key enzymes

- Defining the criteria by which the effects of the chemical environment on the function of biological molecules can be evaluated

For the examination, the student may choose between either a written test or the autonomous preparation of a PowerPoint presentation, which will be reported and discussed orally.

1) The written test consists of answering questions concerning the course program. Subsequently, the student who passes the written test discusses orally with the teacher the contents of the test in order to reach the final evaluation. 

2) The PowerPoint presentation is to be prepared autonomously by the student on a topic of their choice, among those listed in the program, or on a protein of their choice. The presentation is to be based on the autonomous elaboration of literature data and on the structural information acquired through the use of online databases and computer programs taught in class.

Teaching tools

The teaching material projected during classes is made available to the student in electronic format on the course webpage on https://virtuale.unibo.it

The free computer programs ClustalX, NJplot and Pymol* (*educational license only for teaching/learning purposes) is available for download on the same webpage.

Audio recordings of the lectures are allowed, provided that they are made available to all students through the sharing of audio files into restricted areas of the course webpage (to be defined: if you have recordings to share please contact me).

The use of public online databases for proteins sequences and structures, and of bioinformatic tools, is permitted (and welcome!).

Office hours

See the website of Enrico Luchinat