Literature Learning Module

Thermodynamics of the GTP-GDP-operated Conformational Switch of
Selenocysteine-specific Translation Factor SelB

Assessment of Biochemistry/Molecular Biology (BMB) Foundational Concepts

Henry Jakubowski, Ph.D., Professor, Chemistry Department, College of Saint Benedict/Saint John's University

 
05/24/2014

The questions below are based on data, graphs, and figures from the following article:

Thermodynamics of the GTP-GDP-operated Conformational Switch of Selenocysteine-specific Translation Factor SelB. Alena Paleskava, Andrey L. Konevega and Marina V. Rodnina . The Journal of Biological Chemistry, 287, 27906-27912 (2012).  doi: 10.1074/jbc.M112.366120  . 

These guidelines apply to the reuse of articles, figures, charts and photos in the Journal of Biological Chemistry, Molecular & Cellular Proteomics and the Journal of Lipid Research.

These questions may be used to help assess student mastery of key foundational concepts in BMB developed by the American Society for Biochemistry and Molecular Biology (ASBMB) and tested in the new MCAT2015 developed by the American Association of Medical Colleges.  The particular foundational concepts and learning objectives relevant for this particular assessment are listed below.

ASBMB Biochemistry and Molecular Biology Foundational Concepts  -   Detailed Learning Objectives (Excel)

Foundational Concept 1:  Energy is required by and transformed in biological systems

  •  3.  Given a macromolecule, students should be able to explain the contribution of entropy, enthalpy and temperature of a macromolecule and water (associated and in bulk solvent) in a folded versus unfolded state
  • 4.  Given a biological example, students should be able to explain how thermodynamically unfavorable processes can occur.
  • 6. (loosely)  Given entropy, enthalpy and temperature, students should be able to justify why evolutionary selection is constrained by the laws of thermodynamics

Foundational Concept 2:  Macromolecular structure determines function and regulation.

  • 2. Given a list of macromolecules, students should be able to devise an experiment on how they interact or interpret results of experiments on their interactions
  • 3.  Given structural changes of a macromolecule (or ligand), students should be able to predict the impact of structural substitution would have on macromolecule structure and function
  • 4. Given experimental data, students should be able to assess how enzymes facilitate biochemical reactions.

 Foundational Concept 4: . Discovery requires objective measurement, quantitative analysis, and clear communication. 

  •  2. Given a fundamental understanding of BMB concepts, students should be able to formulate experiments and assess the quality of experiments addressing molecular structure, assays of biological function, and isolation / separation of biomolecules.

MCAT 2015:  Foundational Concepts, Detailed Content and Topics (Excel)

Biological and Biochemical Foundations of Living Systems

Foundational Concept 1 : Biomolecules have unique properties that determine how they contribute to the structure and function of cells, and how they participate in the processes necessary to maintain life

  • 1A. Structure and function of proteins and their constituent amino acids

  • 1D.  Principles of bioenergetics and fuel molecule metabolism

Chemical and Physical Foundations of Biological Systems

Foundational Concept 5: The principles that govern chemical interactions and reactions form the basis for a broader understanding of the molecular dynamics of living systems.

  • 5B. Nature of molecules and intermolecular interactions

  • 5D. Structure, function, and reactivity of biologically - relevant molecules

  • 5E. Principles of chemical thermodynamics and kinetics

Scientific Inquiry and Reasoning Skills

  • 1.  Knowledge of Scientific Concepts and Principles; 

  • 2.  Scientific Reasoning and Problem;

  • 3.  Reasoning about the Design and Execution of Research;

  • 4.  Data-based and Statistical Reasoning

Background

Almost every biological event, with some notable exceptions such as visual signal transduction, is initiated by a binding interactions between two molecules.  These interactions are often accompanied by conformational changes before binding (conformational selection) or after binding (induced fit),or both. Binding can be studied using X-ray crystallography or NMR to determine the 3D structure of the individual molecules and the complex, from which conformational changes associated with binding can be inferred.  In addition, binding should also be quantitatively studied to determine dissociation constants, rate constants, and thermodynamics parameters that characterize the interactions.  For the questions below, investigators determined the changes in standard Gibbs Free energy change (DG0), the standard enthalpy change (DH0), the standard entropy change (DS0), and the change in heat capacity (DCp) for the interaction of GDP and GTP with a protein, selenocysteine-specific Translation Factor SelB.  This protein is a translation factor (like elongation factor Tu) which brings selenocysteyl-tRNA (Sec-tRNASec) to the ribosome.  Like EF-Tu,when bound to the A site in the ribosome,  EF-Tu or SelB cleave bound GTP to GDP, leading to its dissociation from the ribosome.  Presumably this would occur through a conformational change in the protein on GTP cleavage.  The study of GTP and GDP-bound conformations of proteins is very important as many signaling events in a cell occur through small G proteins which are active when GTP is bound and inactive when GDP is bound.

Background Reading:

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