New identification tools targeting a rpoB gene fragment located between positions 2300 and 3300 have been developed recently. Therefore, inclusion of the rpoB gene sequence would be useful when describing new bacterial species.”
“Introduction: Tc-99m-TMEOP is a novel heart perfusion radiotracer exhibiting high initial and persistent heart uptake associated with rapid blood and liver clearance. This study aimed at determining the mechanisms of myocardial localization and fast
liver clearance of Tc-99m-TMEOP.
Methods: Subcellular distribution of Tc-99m-TMEOP was determined in excised rat heart tissue Silmitasertib nmr by differential centrifugation. The effect of cyclosporin A on the pharmacokinetic behaviour of Tc-99m-TMEOP was evaluated by both ex vivo biodistribution and in vivo planar imaging studies.
Results: Subcellular distribution studies showed that more than 73% of Tc-99m-TMEOP was associated with the mitochondrial fraction. Comparison with subcellular distribution of Tc-99m-sestamibi showed H 89 no significant difference in the mitochondrial accumulation between the two tracers. Biodistribution studies in the presence of cyclosporin A revealed an increase
in kidneys and liver uptake of Tc-99m-TMEOP, suggesting the involvement of multidrug resistance transporters in determining its pharmacokinetic profile.
Conclusions: The heart uptake mechanism of Tc-99m-TMEOP is similar to that of the other reported monocationic Tc-99m cardiac agents and is associated with its accumulation in the mitochondria. Cyclosporin A studies indicate that the fast liver and kidney clearance kinetics is mediated by P-glycoprotein (Pgp), supporting the potential interest of this radiotracer Z VAD FMK for imaging Pgp function associated with multidrug-resistant tumours. (C) 2012 Elsevier Inc. All rights reserved.”
“Enoyl-acyl carrier protein (ACP) reductases are critical for bacterial type II fatty acid biosynthesis and thus are attractive
targets for developing novel antibiotics. We determined the crystal structure of enoyl ACP reductase (FabK) from Streptococcus pneumoniae at 1.7 angstrom resolution. There was one dimer per asymmetric unit. Each subunit formed a triose phosphate isomerase (TIM) barrel structure, and flavin mononucleotide (FMN) was bound as a cofactor in the active site. The overall structure was similar to the enoyl-ACP reductase (ER) of fungal fatty acid synthase and to 2-nitropropane dioxygenase (2-ND) from Pseudomonas aeruginosa, although there were some differences among these structures. We determined the crystal structure of FabK in complex with a phenylimidazole derivative inhibitor to envision the binding site interactions. The crystal structure reveals that the inhibitor binds to a hydrophobic pocket in the active site of FabK, and this is accompanied by induced-fit movements of two loop regions.