Développement d'un modèle de "deep learning" pour évaluer la sécurité des patients

International audienc

Développement d'un modèle de "deep learning" pour évaluer la sécurité des patients

International audienc

High resolution crystal structure of cAMP dependent protein kinase from Cricetulus griseus

Protein kinases (PKs) are dynamic regulators of numerous cellular processes. Their phosphorylation activity is determined by the conserved kinase core structure, which is maintained by the interaction and dynamics with associated domains or interacting proteins. The prototype enzyme for investigations to understand the activity and regulation of PKs is the catalytic subunit of cAMP-dependent protein kinase (PKAc). Major effects of functional regulation and ligand binding are driven by only minor structural modulations in protein–protein interactions. In order to resolve such minor structural differences, very high resolution structures are required. Here, the high-resolution X-ray structure of PKAc from Cricetulus griseus is reported

Structure and Biophysical Characterization of the S Adenosylmethionine dependent O Methyltransferase PaMTH1, a Putative Enzyme Accumulating during Senescence of Podospora anserina

Low levels of reactive oxygen species (ROS) act as important signaling molecules, but in excess they can damage biomolecules. ROS regulation is therefore of key importance. Several polyphenols in general and flavonoids in particular have the potential to generate hydroxyl radicals, the most hazardous among all ROS. However, the generation of a hydroxyl radical and subsequent ROS formation can be prevented by methylation of the hydroxyl group of the flavonoids. O-Methylation is performed by O-methyltransferases, members of the S-adenosyl-l-methionine (SAM)-dependent O-methyltransferase superfamily involved in the secondary metabolism of many species across all kingdoms. In the filamentous fungus Podospora anserina, a well established aging model, the O-methyltransferase (PaMTH1) was reported to accumulate in total and mitochondrial protein extracts during aging. In vitro functional studies revealed flavonoids and in particular myricetin as its potential substrate. The molecular architecture of PaMTH1 and the mechanism of the methyl transfer reaction remain unknown. Here, we report the crystal structures of PaMTH1 apoenzyme, PaMTH1-SAM (co-factor), and PaMTH1-S-adenosyl homocysteine (by-product) co-complexes refined to 2.0, 1.9, and 1.9 Å, respectively. PaMTH1 forms a tight dimer through swapping of the N termini. Each monomer adopts the Rossmann fold typical for many SAM-binding methyltransferases. Structural comparisons between different O-methyltransferases reveal a strikingly similar co-factor binding pocket but differences in the substrate binding pocket, indicating specific molecular determinants required for substrate selection. Furthermore, using NMR, mass spectrometry, and site-directed active site mutagenesis, we show that PaMTH1 catalyzes the transfer of the methyl group from SAM to one hydroxyl group of the myricetin in a cation-dependent manner

Molecular Mechanism of SSR128129E, an Extracellularly Acting, Small-Molecule, Allosteric Inhibitor of FGF Receptor Signaling (vol 23, pg 489, 2013)

© 2016 Elsevier Inc. (Cancer Cell 23, 489–501, April 15, 2013) In Figure 2F, the authors failed to highlight clearly that there is a split in the western blot (all rows) between the “0” and “0.1” condition. Even though all samples were run in the same experiment on the same blot, the image was split to remove samples that were simultaneously analyzed but irrelevant for this study. In the corrected Figure 2 F, the authors have now clearly separated both parts of the western blot. In Figure 5B, the image of the western blot showing total FGFR2 for the HEK293-FGFR2Y328D cell line was mistakenly replaced with the image of the western blot showing total FGFR2 for the HEK293-FGFR2WT cell line from Figure 5A. In the corrected Figure 5B, the authors have included the correct image of the western blot showing total FGFR2 for the HEK293-FGFR2Y328D cell line. The corrected Figure 2 and Figure 5 are included below. The authors apologize for any confusion these mistakes may have caused the readers.Correctionstatus: publishe