Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey

Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Session I Abstracts

Organism-adapted Specificity of Allosteric Regulation of Central Metabolic Enzymes in Lactic Acid Bacteria Rebecca C. Wade 1,2 , Stefan Henrich 1 , Anna Feldman-Salit 1,2 , Nadine Veith 1,2 , Ursula Kummer 2 , Vlad Cojocaru 1,3 . 2 Heidelberg University, Heidelberg, Germany, 1 Heidelberg Institute for Theoretical Studies, Heidelberg, Germany, 3 Max Planck Institute for Molecular Biomedicine, Münster, Germany. Allosteric regulation provides one important strategy for adaptation of an organism to its environment and for cross-talk between metabolic pathways. Lactic acid bacteria have adapted to a range of different environments where they have diverse effects ranging from being antibiotic- resistant pathogens causing severe disease to healthy probiotics used in the food industry. We focused on the enzymes, lactate dehydrogenase [1] and pyruvate kinase [2], which both play central roles in the metabolism of lactic acid bacteria. These enzymes need to react quickly to changes in the environment and, therefore, their activity is strictly regulated. We developed and applied computational techniques to predict the allosteric modulators that are responsible for the activation or inhibition of these enzymes in four different bacteria, and to explore the effects of environmental conditions on the allosteric regulation. The studies of both proteins show how enzymes with high sequence similarity can have subtle but significant differences in allosteric regulation in related organisms that must function in different environments. [1] Anna Feldman-Salit, Silvio Hering, Hanan L Messhia, Nadine Veith, Vlad Cojocaru, Antje Sieg, Hans V. Westerhoff, Bernd Kriekemeyer, Rebecca C Wade and Tomas Fiedler. Regulation of the activity of lactate dehydrogenases from four lactic acid bacteria. J. Biol. Chem., (2013) 288:21295-306. [2] Nadine Veith, Anna Feldman-Salit, Vlad Cojocaru, Stefan Henrich, Ursula Kummer and Rebecca C Wade. Organism-adapted specificity of the allosteric regulation of pyruvate kinase in lactic acid bacteria. PLoS Comput Biol., (2013) 9:e1003159. Funding from the Klaus Tschira Foundation and the German Federal Ministry of Education and Research (BMBF, SysMO-LAB2 Projects 0313979A, 0315788B) is gratefully acknowledged.

13