Role of the ribosome in protein folding

In all organisms, the ribosome synthesizes and folds full length polypeptide chains into active three-dimensional conformations. The nascent protein goes through two major interactions, first with the ribosome which synthesizes the polypeptide chain and holds it for a considerable length of time, and then with the chaperones. Some of the chaperones are found in solution as well as associated to the ribosome. A number of in vitro and in vivo experiments revealed that the nascent protein folds through specific interactions of some amino acids with the nucleotides in the peptidyl transferase center (PTC) in the large ribosomal subunit. The mechanism of this folding differs from self-folding. In this article, we highlight the folding of nascent proteins on the ribosome and the influence of chaperones etc. on protein folding

Immunogenicity and safety of live attenuated hepatitis A Vaccine: a multicentric study

Objective: To evaluate immunogenicity and tolerability of single dose live attenuated injectable hepatitis A vaccine in four metropolitan cities of India. Methods: Live attenuated hepatitis A vaccine was administered to 505 children aged 18-60 months in four centers across India. Immunogenicity of the vaccine was assessed by estimation of anti-HAV antibody titer at 6 weeks and 6 months following administration of the vaccine. Safety evaluation of the vaccine was also done during the visits. Results: At 6 weeks, 480 subjects (95%) came for the follow-up and 411 (81.4%) subjects reported at the end of 6 months. The geometric mean titer (GMT) of anti-HAV antibody of the subjects who did not have the seroprotective titer at the baseline were assessed at 6 weeks and 6 months which was 81.04 mIU/ml and 150.66 mIU/ml respectively. At 6 weeks, 95.1% seroconverted and at the end of 6 months, 97.9% had seroconverted. Both solicited and unsolicited vaccine-induced local and systemic adverse events were insignificant at all the centers, except swelling and induration in a few. Conclusion: Live attenuated injectable hepatitis A vaccine was immunogenic and tolerable with minimal reactogenecity, in this study of single dose schedule. Safety profile was also satisfactory in the study population

Calcium ion incorporated hydrous iron(III) oxide: synthesis, characterization, and property exploitation towards water remediation from arsenite and fluoride

Calcium ion-incorporated hydrous iron(III) oxide (CIHIO) samples have been prepared aiming investigation of efficiency enhancement on arsenic and fluoride adsorption of hydrous iron(III) oxide (HIO). Characterization of the optimized product with various analytical tools confirms that CIHIO is microcrystalline and mesoporous (pore width, 26.97 Å; pore diameter, 27.742 Å with pore volume 0.18 cm3 g−1 ) material. Increase of the BET surface area (> 60%) of CIHIO (269.61 m2 g−1 ) relative to HIO (165.6 m2 g−1 ) is noticeable. CIHIO particles are estimated to be ~ 50 nm from AFM and TEM analyses. Although the pH optimized for arsenite and fluoride adsorptions are different, the efficiencies of CIHIO towards their adsorption are very good at pH 6.5 (pHzpc). The adsorption kinetics and equilibrium data of either tested species agree well, respectively, with pseudo-second order model and Langmuir monolayer adsorption phenomenon. Langmuir capacities (mg g−1 at 303 K) estimated are 29.07 and 25.57, respectively, for arsenite and fluoride. The spontaneity of adsorption reactions (ΔG0 = − 18.02 to − 20.12 kJ mol−1 for arsenite; − 0.2523 to − 3.352 kJ mol−1 for fluoride) are the consequence of entropy parameter. The phosphate ion (1 mM) compared to others influenced adversely the arsenite and/or fluoride adsorption reactions. CIHIO (2.0 g L−1 ) is capable to abstract arsenite or fluoride above 90% from their solution (0 to 5.0 mg L−1 ). Mechanism assessment revealed that the adsorption of arsenite occurs via chelation, while of fluoride occurs with ion-exchange

Synthesis, Characterization, and Biological Evaluation of Some 3d-Metal Complexes of Schiff Base Derived from Xipamide Drug

The present paper deals with the synthesis and characterization of metal complexes of Schiff base derived from xipamide, a diuretic drug. The bidentate ligand is derived from the inserted condensation of 5-aminosulfonyl-4-chloro-N-2,6-dimethyl phenyl-2-hydroxybenzamide (Xipamide) with salicylaldehyde in a 1 : 1 molar ratio. Using this bidentate ligand, complexes of Hg(II), Zn(II), and VO(IV) with general formula ML2 have been synthesized. The synthesized complexes were characterized by several techniques using molar conductance, elemental analysis, magnetic susceptibility, FT-IR spectroscopy, electronic spectra, mass spectra, and particle size analysis. The elemental analysis data suggest the stoichiometry to be 1 : 2 [M : L]. All the complexes are nonelectrolytic in nature as suggested by molar conductance measurements. Infrared spectral data indicate the coordination between the ligand and the central metal ion through deprotonated phenolic oxygen and azomethine nitrogen atoms. Spectral studies suggest tetrahedral geometry for Hg(II), Zn(II) complexes, and square pyramidal geometry for VO(IV) complex. The pure drug, synthesized ligand, and metal complexes were screened for their antifungal activities against Aspergillus niger and Aspergillus flavus. The ligand and its Hg(II) and VO(IV) complexes were screened for their diuretic activity too

Insight to structural subsite recognition in plant thiol protease-inhibitor complexes : Understanding the basis of differential inhibition and the role of water

<p>Abstract</p> <p>Background</p> <p>This work represents an extensive MD simulation / water-dynamics studies on a series of complexes of inhibitors (leupeptin, E-64, E-64-C, ZPACK) and plant cysteine proteases (actinidin, caricain, chymopapain, calotropin DI) of papain family to understand the various interactions, water binding mode, factors influencing it and the structural basis of differential inhibition.</p> <p>Results</p> <p>The tertiary structure of the enzyme-inhibitor complexes were built by visual interactive modeling and energy minimization followed by dynamic simulation of 120 ps in water environment. DASA study with and without the inhibitor revealed the potential subsite residues involved in inhibition. Though the interaction involving main chain atoms are similar, critical inspection of the complexes reveal significant differences in the side chain interactions in S₂-P₂ and S₃-P₃ pairs due to sequence differences in the equivalent positions of respective subsites leading to differential inhibition.</p> <p>Conclusion</p> <p>The key finding of the study is a conserved site of a water molecule near oxyanion hole of the enzyme active site, which is found in all the modeled complexes and in most crystal structures of papain family either native or complexed. Conserved water molecules at the ligand binding sites of these homologous proteins suggest the structural importance of the water, which changes the conventional definition of chemical geometry of inhibitor binding domain, its shape and complimentarity. The water mediated recognition of inhibitor to enzyme subsites (P_n...H₂O....S_n) of leupeptin acetyl oxygen to caricain, chymopapain and calotropinDI is an additional information and offer valuable insight to potent inhibitor design.</p