MmoS binds an FAD cofactor within its N-terminal tandem Per-Arnt-Sim (PAS) domains, suggesting that it functions as a redox sensor. The crystal structure of the MmoS tandem PAS domains, designated PAS-A and PAS-B, has been determined to 2.34 angstrom resolution. Both domains adopt the typical PAS domain alpha/beta topology and are structurally similar. The two domains are linked by a long alpha helix and do not interact with one another. The FAD cofactor is housed solely within PAS-A and is stabilized by an extended Lazertinib Protein Tyrosine Kinase inhibitor hydrogen bonding network. The overall fold of PAS-A is similar to those of other

flavin-containing PAS domains, but homodimeric interactions in other structures are not observed in the MmoS sensor, which crystallized as a monomer. The structure both provides new insight into the architecture of tandem PAS domains and Suggests specific residues that may play a role

in MmoS FAD redox chemistry and subsequent signal transduction.”
“Objective: Exposure to cigarette BMS-345541 smoke in adult smokers (SM) can be determined by measuring urinary excretion of selected smoke constituents or metabolites. Complete 24h urine collections are difficult to achieve in ambulatory clinical studies; therefore spot urine (SU) might be a useful alternative. The objective of this study was to evaluate the optimum time for SU collections, and to predict 24h urine biomarker excretion from SU collections.\n\nMethods: SU samples were collected at three time points (early morning, post-lunch and evening) along with 24h collections in 37 healthy adult smokers. Nicotine and its five metabolites (nicotine equivalents, selleck screening library NE), metabolites of NNK (NNAL), pyrene (1-OHP), acrolein (HPMA), benzene (S-PMA) and butadiene (MHBMA) were measured in 24h and SU samples. Correlation and agreement between creatinine-adjusted SU and 24h urine collections were determined from the Pearson product-moment correlation, Bland-Altman and Lin’s concordance correlation

analyses. A random effect regression model was used to calculate the 24h biomarker excretion from SU collections.\n\nResults: There were no significant differences (p > 0.05) between the three SU collections for the selected biomarkers of exposure except for 3-HPMA, which showed a diurnal variation. Good correlation and statistical agreements were observed for creatinine-adjusted SU (all three time points) and 24h for most of the selected biomarkers. 24h biomarker excretion could be estimated for most of the biomarkers based on the regression model, with the early morning SU collections giving the best results for tobacco specific biomarkers NE (R-2 = 0.66) and NNAL (R-2 = 0.6).\n\nConclusions: SU is a useful alternative to 24h urine collections for most of the selected biomarkers of exposure to cigarette smoke.