Crystal Structure, Spectral investigations, DFT and Antimicrobial activity of Brucinium Benzilate (BBA)

The unreported Brucinium Benzilate (BBA) crystal and hirshfeld surface analysis indicated the influence of intramolecular hydrogen bonding network. The protonation of tertiary nitrogen occurs as it is most basic. The protonated N-H+ proton was observed at 7.08 ppm and the benzilate carbon COO- at 178.41 ppm. Molecular electrostatic potential (MEP) studies indicated the electron-rich and electron-deficient sites in the molecule for understanding BBA interaction with an enzyme. Frontier molecular orbital (FMO) studies indicated that it is thermodynamically stable and HOMO-LUMO energy gap was found to be 4.454 eV. The highest interaction as the energy (322.86 kcal/mol) between tertiary ammonium N(LP) and H+. The compound showed the inhibition of Bacillus cereus and Salmonella typhimurium bacteria. ADMET properties indicated that BBA has drug characteristics in binding plasma protein.

Gelsolin expression in liver, spleen and blood plasma provides insights into its function in mice following acute insults

Background: Gelsolin (GSN) is an actin-binding plasma protein with a pivotal role in the systemic response to acute tissue damage. The present study investigated GSN expression in the liver, spleen and blood serum in mice after burn. Method: A murine model of thermal injury was selected, and the animals were sacrificed at 8, 24, 48 and 72 h after injury. Real-time quantitative polymerase chain reaction (RT-PCR) was performed to determine the messenger RNA (mRNA) expression of GSN, and GSN protein expression was determined by enzyme-linked immunosorbent assay (ELISA). Results: We found that GSN mRNA and protein were expressed in the liver, spleen and blood serum of the mice. GSN expression in these tissues was the lowest among the tested time points at 8 h after burn injury. The mortality within 72 h among the mice subjected to burn injury was significantly lower in those treated with GSN than in those not treated with GSN. Treatment with GSN markedly increased the GSN levels in the liver, spleen and blood serum after injury. Conclusion: These results indicated that GSN treatment may affect the outcome of thermal injury via changes in the GSN content of multiple tissues.

Haptoglobin-related protein is a high-affinity hemoglobin-binding plasma protein

Haptoglobin-related protein (Hpr) is a primate-specific plasma protein associated with apolipoprotein L-I (apoL-I)-containing high-density lipoprotein (HDL) particles shown to be a part of the innate immune defense. Despite the assumption hitherto that Hpr does not bind to hemoglobin, the present study revealed that recombinant Hpr binds hemoglobin as efficiently as haptoglobin (Hp). However, in contrast to Hp, Hpr did not promote any high-affinity binding to the scavenger receptor CD163. Binding of hemoglobin to circulating native Hpr incorporated into the HDL fraction was indicated by hemoglobin-affinity precipitation of plasma Hpr together with apoL-I. In conclusion, plasma has 2 high-affinity hemoglobin-binding haptoglobins instead of one, but only Hp-hemoglobin complexes are efficiently recognized by CD163. Circulating Hpr-bound hemoglobin should therefore be taken into consideration when measuring “free” plasma hemoglobin. Furthermore, Hpr-bound hemoglobin might contribute to the biologic activity of the circulating apoL-I/Hpr-containing HDL particles.

Specificity Determinants in the Interaction of Apolipoprotein(a) Kringles with Tetranectin and LDL

Lipoprotein(a) is composed of low density lipoprotein and apolipoprotein(a). Apolipoprotein(a) has evolved from plasminogen and contains 10 different plasminogen kringle 4 homologous domains [KIV(1 110)]. Previous studies indicated that lipoprotein(a) noncovalently binds the Nterminal region of lipoprotein B100 and the plasminogen kringle 4 binding plasma protein tetranectin. In this study recombinant KIV(2), KIV(7) and KIV(10) derived from apolipoprotein(a) were produced in E. coli and the binding to tetranectin and low density lipoprotein was examined. Only KIV(10) bound to tetranectin and binding was similar to that of plasminogen kringle 4 to tetranectin. Only KIV(7) bound to LDL. In order to identify the residues responsible for the difference in specificity between KIV(7) and KIV(10), a number of surfaceexposed residues located around the lysine binding clefts were exchanged. Ligand binding analysis of these derivatives showed that Y62, and to a minor extent W32 and E56, of KIV(7) are important for LDL binding to KIV(7), whereas R32 and D56 of KIV(10) are required for tetranectin binding of KIV(10).