Introduction to Structural Biochemistry

Year
2
Academic year
2024-2025
Code
01004574
Subject Area
Biochemistry
Language of Instruction
Portuguese
Mode of Delivery
Face-to-face
Duration
SEMESTRIAL
ECTS Credits
3.0
Type
Compulsory
Level
1st Cycle Studies

Recommended Prerequisites

Biochemistry of Proteins, Nucleic Acids and Lipids, Inorganic Biochemistry, Biochemistry Physics, Biochemistry of Metabolism,  Biomolecular Spectroscopy. The students should know the structure and reactivity of biological molecules, their equilibria in solution, thermodynamic and kinetic stability, the role of metal ions in their structures, mechanistic aspects, structure-function relationship, as well as spectrsocopic techniques used for structure elucidation.

Teaching Methods

Theoretical - subjects are presented using attractive slides and informatics devices (specific internet links and videos). Active participation of the students is encouraged: clarify doubts, discuss  items, apply knowledge to specific problems and situations.

Lab classes (dry labs) - students learn how to use programs to process and interpret 2D NMR spectra, visualize structures and obtain structural and mechanistic data of biological polymers and supramolecular interactions (weblabs); resolution of questions and report. Reading and interpretation of scientific papers in english.

Learning Outcomes

This CU aims at the students:

- know the basic and advanced concepts about the structure  of proteins, nucleic acids and supramolecular biological complexes, such as protein-ligand, protein-protein, protein-nucleic acid.

-interpret structure-function relationship of proteins

-know the main techniques used to determine the structure of biological structures, such as X-ray Diffraction, multidimensional NMR spectroscopy, techniques to interpret and validate experimental data

-get familiar with the use of available on line tools for molecular modeling

At the end of this CU the student should have a synthetic and analytical knowledgement and be able to obtain and interpret experimental data to understand structure-function relationship of biological macromolecules.

Work Placement(s)

No

Syllabus

Determination of 3D structure of proteins- X-ray crystallography. Crystallization of proteins; X-ray diffraction; measurements and experimental data analysis; electron density; refinement and temperature factor; acquisition of a structural model. Interpretation of structural data: validation; conformational analysis; quality of the model and precision of the 3D structure; comparison of conformational states in crystalline structures and in solution; structural data bases.

Multidimensional NMR: structural information: angles, distances, chemical environment; data acquisition and spectral assignment; bi- and tridimensional methods. Methodology for protein structure determination by NMR (small <15 kDa and large >15kDa). Isotopic labeling 2H, 13C, 15N.

Structure and function of proteins –structure-function relationship. Intercations protein-ligand, protein-protein and protein-nuclei acid. Formation of macromolecular complexes. Drug design.

Head Lecturer(s)

Irina de Sousa Moreira

Assessment Methods

Assessment
Laboratory work or Field work: 25.0%
Project: 25.0%
Exam: 50.0%

Bibliography

C.-I. and J. Tooze (1999) Introduction to Protein Structure” Branden, Garland Pub.

A.M. Lesk (2001) Introduction to Protein Architecture: The Structural Biology of Proteins, Oxford U.P.

G.E. Schultz and R.H. Schirmer (1988) Principles of Protein Structure, Springer-Verlag, N.Y.

G. Rhodes (2000) Crystallography Made Crystal Clear- A Guide for users of Macromolecular Models, 2nd ed., Academic     Press: San Diego, London.

T.L. Blundell and L. N. Johnson (1976) Protein Crystallography, Academic Press, London, 1976

J. Drenth (1994) Principles of Protein X-Ray Crystallography, Springer-Verlag, NewYork

J.N.S Evans (1995) Biomolecular NMR Spectroscopy, Oxford University Press.

G.M. Clore and A. M. Gronenborn (1993) NMR of Proteins – Topics on Molecular and Structural Biology, CRC Pres.

G.S. Rule and T.K. Hitchens (2005) Fundamentals of Protein NMR Spectroscopy in Structural Biology, Springer

P.E. Bourne (Ed) and  H. Weissig (Ed) (2003) Structural Bioinformatics