Structure-function relations studies

within multi-enzymatic complexes

 We study enzymes made of subunits within large complexes. These complexes play their role at different levels either for an easier transport of ligands of an enzyme to its neighbor, or to allow the blocking or activation of a particular metabolic pathway using allosteric effectors (small messenger molecules capable of modulating enzymatic activity upon fixation on the complex).
Here we compute the 3D reconstruction of these biological "nano-machines", using molecular markers (antibody, or gold markers functionalized to bind to free thiols or poly-histidines sequences) to locate each subunit of the complex.
Then, we study their architecture with the highest possible degree of accuracy (subnanometric resolution), and by blocking them in active or inhibited conformations, in the presence of allosteric effectors or specific inhibitors.
Combined with molecular modeling methods such as profile-based sequence comparison, Hydrophobic Cluster Analysis (HCA, See Sequences and Folding Team), these approaches allow to propose functional models of large marocomolecular assemblies at the atomic level.