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Purpose: Loganin, one of the two main iridoid glycosides in Cornus officinalisSieb et Zucc, has been reported to exhibit many biological activities such as immune modulation, as well as anti-inflammatory and anti-shock effects. This study was designed to evaluate the pharmacokinetics of loganin, administered intravenously (5, 10, 20 and 50 mg/kg) and orally (20, 50, 100 and 200 mg/kg), in rats. Methods: To evaluate its hepatic and gastrointestinal first-pass effects, loganin was administered intraportally, intragastrically and intraduodenally to rats. Results: Following intravenous administration of 5–50 mg/kg loganin, a linear relationship was observed between the total area under the plasma concentration–time curve from zero to infinity (AUC) and loganin dose, with ~ 19% of the administered dose excreted in the urine. AUCs following oral administration of 20–200 mg/kg loganin were dose-independent, with the extent of absolute oral bioavailability (F) being approximately 4.87%. The AUC of loganin was significantly lower by 90.6% after intraduodenal than intraportal administration, but did not differ between intragastric and intraduodenal administration. The AUC was also significantly lower by 52.7% after intraportal, compared to intravenous, administration, suggesting that the hepatic first-pass effect on loganin after entering the portal vein was approximately 4.95% of the oral dose. Conclusion: Taken together, our data suggest that the low Fof loganin in rats was due exclusively to its high intestinal first-pass metabolism.

The periplasmic domain of OmpA from Acinetobacter baumannii(AbOmpA-PD) binds to diaminopimelate and anchors the outer membrane to the peptidoglycan layer in the cell wall. Although the crystal structure of AbOmpA-PD with its ligands has been reported, the mechanism of ligand-mediated folding of AbOmpA remains elusive. Here, we report that in vitro refolded apo-AbOmpA-PD in the absence of ligand exists as a mixture of two partially folded forms in solution: mostly unfolded (apo-state I) and hololike (apo-state II) states. Binding of the diaminopimelate or glycine ligand induced complete folding of AbOmpA-PD. The apo-state I was highly flexible and contained some secondary structural elements, whereas the apo-state II closely resembled the holo-state in terms of both structure and backbone dynamics, except for the ligand-binding region. 15N-relaxation-dispersion analyses for apo-state II revealed substantial motion on a millisecond timescale of residues in the H3 helix near the ligand-binding site, with this motion disappearing upon ligand binding. These results provide an insight into the ligand-mediated folding mechanism of AbOmpA-PD in solution.

The binding of SeqA protein to hemimethylated GATC sequences is important in the negative modulation of chromosomal initiation at oriC, and in the formation of SeqA foci necessary for Escherichia colichromosome segregation. Using gel-filtration chromotography and glycerol gradient sedimentation, we demonstrate that SeqA exists as a homotetramer. SeqA tetramers are able to aggregate or multimerize in a reversible, concentration-dependent manner. Using a bacterial two-hybrid system, we demonstrate that the N-terminal region of SeqA, especifically the 9th amino acid residue, glutamic acid, is required for functional SeqA-SeqA interaction. Although the SeqA(E9K) mutant protein, containing lysine rather than glutamic acid at the 9th amino acid residue, exists as a tetramer, the mutant protein binds to hemimethylated DNA with altered binding patterns as compared with wild-type SeqA. Aggregates of SeqA(E9K) are defective in hemimethylated DNA binding. Here we demonstrate that proper interaction between SeqA tetramers is required for both hemimethylated DNA binding and formation of active aggregates. SeqA tetramers and aggregates might be involved in the formation of SeqA foci required for the segregation of chromosomal DNA as well as the regulation of chromosomal initiation.