Catégorie d'actualités: significant publications

CBM researchers have created the first method for detecting non-covalent complexes of biomolecules by MALDI mass spectrometry based on liquid deposits

The success of this method relies on the use of nonvolatile liquid matrices, which avoids the passage through the solid phase conventionally used in MALDI and the denaturation of the non-covalent assemblies. By their increased viscosity, these matrices also have the advantage of better mimicking the cluttered environments of living organisms.
The reliability of this method has been shown for non-covalent protein protein and ligand protein systems. This new approach could be used for screening of therapeutic protein ligands and facilitating the analysis of membrane protein complexes by mass spectrometry.

The first computational method to predict Rho-dependent termination of transcription.

Rho-dependent termination is a specific bacterial mechanism, which plays a major role in gene expression and maintenance of genomic integrity. This is an important mechanism for the fast adaptation of bacteria to environmental changes or stresses. Although Rho-dependent termination sites are very diverse and without a real consensus sequence, CBM researchers have identified dozens of quantitative sequence descriptors (eg% C and% G) that, taken collectively, provide good prediction of the sites of Rho action in the model genomes of Escherichia coli and Salmonella (85% success rate).

This work was published in the journal Nucleic Acids Research.

 

Molecular traps for DNA repair enzymes, a way for cancers and aging diseases therapies

Combining chemical synthesis of derivatives DNA molecules, designed to mimic small and large lesions, with comparative structural analysis of Fpg bound to damaged DNA, scientist from CBM have established the molecular basis for formation of an unproductive but stable complex between Fpg and the bulky DNA lesion. They suggest that formation of such abortive complex inhibits DNA repair processes, thus explaining the long persistence of these lesions observed in vivo their associated cell deleterious effects. Selective inhibition of Fpg and hOgg1 by bulky DNA lesions and their synthetic derivatives can, for example, be used for treating subjects having disorders associated either with excessive cell proliferation, such as in the treatment of various cancers, or with aging (degenerative diseases such as Alzheimer and Huntington).

References :
Coste, F., Ober, M., Le Bihan, Y.-V., Izquierdo, M.A., Hervouet, N., Carell, T. and Castaing, B. “Bacterial base excision repair enzyme Fpg recognizes bulky N7-substituted-FapydG lesion via unproductive binding mode.” Chemistry & Biology (2008) 15, 706-717

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