Morphological profiling of environmental chemicals enables efficient and untargeted exploration of combination effects.

Environmental chemicals are commonly studied one at a time, and there is a need to advance our understanding of the effect of exposure to their combinations. Here we apply high-content microscopy imaging of cells stained with multiplexed dyes (Cell Painting) to profile the effects of Cetyltrimethylammonium bromide (CTAB), Bisphenol A (BPA), and Dibutyltin dilaurate (DBTDL) exposure on four human cell lines; both individually and in all combinations. We show that morphological features can be used with multivariate data analysis to discern between exposures from individual compounds, concentrations, and combinations.

Mechanism of mycolic acid cyclopropane synthase: a theoretical study.

The reaction mechanism of mycolic acid cyclopropane synthase is investigated using hybrid density functional theory. The direct methylation mechanism is examined with a large model of the active site constructed on the basis of the crystal structure of the native enzyme. The important active site residue Glu140 is modeled in both ionized and neutral forms.

Quantum chemical modeling of enzymatic reactions: the case of histone lysine methyltransferase.

Quantum chemical cluster models of enzyme active sites are today an important and powerful tool in the study of various aspects of enzymatic reactivity. This methodology has been applied to a wide spectrum of reactions and many important mechanistic problems have been solved. Herein, we report a systematic study of the reaction mechanism of the histone lysine methyltransferase (HKMT) SET7/9 enzyme, which catalyzes the methylation of the N-terminal histone tail of the chromatin structure.

The reaction mechanism of phenylethanolamine N-methyltransferase: a density functional theory study.

Hybrid density functional theory methods were used to investigate the reaction mechanism of human phenylethanolamine N-methyltransferase (hPNMT). This enzyme catalyzes the S-adenosyl-L-methionine-dependent conversion of norepinephrine to epinephrine, which constitutes the terminal step in the catecholamine biosynthesis. Several models of the active site were constructed based on the X-ray structure.