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Rishikesh S. Parulekar Sagar H. Barage Chidambar B. Jalkute Maruti J. Dhanavade Prayagraj M. Fandilolu Kailas D. Sonawane 《The protein journal》2013,32(6):467-476
Mycobacterium tuberculosis is a Gram positive, acid-fast bacteria belonging to genus Mycobacterium, is the leading causative agent of most cases of tuberculosis. The pathogenicity of the bacteria is enhanced by its developed DNA repair mechanism which consists of machineries such as nucleotide excision repair. Nucleotide excision repair consists of excinuclease protein UvrABC endonuclease, multi-enzymatic complex which carries out repair of damaged DNA in sequential manner. UvrC protein is a part of this complex and thus helps to repair the damaged DNA of M. tuberculosis. Hence, structural bioinformatics study of UvrC protein from M. tuberculosis was carried out using homology modeling and molecular docking techniques. Assessment of the reliability of the homology model was carried out by predicting its secondary structure along with its model validation. The predicted structure was docked with the ATP and the interacting amino acid residues of UvrC protein with the ATP were found to be TRP539, PHE89, GLU536, ILE402 and ARG575. The binding of UvrC protein with the DNA showed two different domains. The residues from domain I of the protein VAL526, THR524 and LEU521 interact with the DNA whereas, amino acids interacting from the domain II of the UvrC protein included ARG597, GLU595, GLY594 and GLY592 residues. This predicted model could be useful to design new inhibitors of UvrC enzyme to prevent pathogenesis of Mycobacterium and so the tuberculosis. 相似文献
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Chetan E. Chitnis Paushali Mukherjee Shantanu Mehta Syed Shams Yazdani Shikha Dhawan Ahmad Rushdi Shakri Rukmini Bharadwaj Puneet Kumar Gupta Dhiraj Hans Suman Mazumdar Bijender Singh Sanjeev Kumar Gaurav Pandey Varsha Parulekar Nathalie Imbault Preethi Shivyogi Girish Godbole Krishna Mohan Odile Leroy Kavita Singh Virander S. Chauhan 《PloS one》2015,10(4)
Background
A phase I randomised, controlled, single blind, dose escalation trial was conducted to evaluate safety and immunogenicity of JAIVAC-1, a recombinant blood stage vaccine candidate against Plasmodium falciparum malaria, composed of a physical mixture of two recombinant proteins, PfMSP-119, the 19 kD conserved, C-terminal region of PfMSP-1 and PfF2 the receptor-binding F2 domain of EBA175.Method
Healthy malaria naïve Indian male subjects aged 18–45 years were recruited from the volunteer database of study site. Fifteen subjects in each cohort, randomised in a ratio of 2:1 and meeting the protocol specific eligibility criteria, were vaccinated either with three doses (10μg, 25μg and 50μg of each antigen) of JAIVAC-1 formulated with adjuvant Montanide ISA 720 or with standard dosage of Hepatitis B vaccine. Each subject received the assigned vaccine in the deltoid muscle of the upper arms on Day 0, Day 28 and Day 180.Results
JAIVAC-1 was well tolerated and no serious adverse event was observed. All JAIVAC-1 subjects sero-converted for PfF2 but elicited poor immune response to PfMSP-119. Dose-response relationship was observed between vaccine dose of PfF2 and antibody response. The antibodies against PfF2 were predominantly of IgG1 and IgG3 isotype. Sera from JAIVAC-1 subjects reacted with late schizonts in a punctate pattern in immunofluorescence assays. Purified IgG from JAIVAC-1 sera displayed significant growth inhibitory activity against Plasmodium falciparum CAMP strain.Conclusion
Antigen PfF2 should be retained as a component of a recombinant malaria vaccine but PfMSP-119 construct needs to be optimised to improve its immunogenicity.Trial Registration
Clinical Trial Registry, India CTRI/2010/091/000301 相似文献45.
Maria Ximena Sosa I. K. Ashok Sivakumar Samantha Maragh Vamsi Veeramachaneni Ramesh Hariharan Minothi Parulekar Karin M. Fredrikson Timothy T. Harkins Jeffrey Lin Andrew B. Feldman Pramila Tata Georg B. Ehret Aravinda Chakravarti 《PLoS computational biology》2012,8(10)
We describe methods for rapid sequencing of the entire human mitochondrial genome (mtgenome), which involve long-range PCR for specific amplification of the mtgenome, pyrosequencing, quantitative mapping of sequence reads to identify sequence variants and heteroplasmy, as well as de novo sequence assembly. These methods have been used to study 40 publicly available HapMap samples of European (CEU) and African (YRI) ancestry to demonstrate a sequencing error rate <5.63×10−4, nucleotide diversity of 1.6×10−3 for CEU and 3.7×10−3 for YRI, patterns of sequence variation consistent with earlier studies, but a higher rate of heteroplasmy varying between 10% and 50%. These results demonstrate that next-generation sequencing technologies allow interrogation of the mitochondrial genome in greater depth than previously possible which may be of value in biology and medicine. 相似文献
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Shanmuga Priya V. G. Swaminathan Priya Muddapur Uday M. Fandilolu Prayagraj M. Parulekar Rishikesh S. Sonawane Kailas D. 《International journal of peptide research and therapeutics》2019,25(2):697-709
International Journal of Peptide Research and Therapeutics - Inhibition of protein–protein interaction is considered as an innovative approach in the drug development field. In the present... 相似文献
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A nearly universal feature of intron sequences is that even closely related
species exhibit a large number of insertion/deletion differences. The goal
of the analysis described here is to test whether the observed pattern of
insertion/deletion events in the genealogy of the myosin alkali light chain
(Mlc1) gene is consistent with neutrality, and if not, to determine the
underlying forces of evolutionary change. Mlc1 pre-mRNA is alternatively
spliced, and one constraint is that signals necessary for
tissue-specificity of directed splicing must be conserved. If the total
length of an intron is functionally constrained, then the distribution of
indels on branches of the gene genealogy should reflect a departure from
randomness. Here we perform a phylogenetic analysis, inferring ancestral
states wherever possible on a phylogeny of 29 alleles of Mlc1 from six
species of Drosophila. Observed patterns of indels on the genealogy were
compared to those from simulated data, with the result that we cannot
reject the null hypothesis of neutrality. A clear departure from a neutral
prediction was seen in the excess folding free energy predicted for the
introns flanking the alternatively spliced exon. Relative rate tests also
suggest a retardation in the rate of Mlc1 sequence evolution in the
simulans clade.
相似文献
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Macrofauna of seagrass community in the five Lakshadweep atolls were studied and compared. The associated epifaunal and infaunal taxa comprising nine major taxonomic groups, showed significant differences in the total number of individuals (1041–8411 m–2) among sites and habitats. The density of macrofauna was directly related to mean macrophytic biomass (405–895 g wet wt. m–2). The fauna was dominated by epifaunal polychaetes, amphipods and isopods in the vegetated areas. When compared with the density of nearby unvegetated areas
, seagrass meadows harbour a denser and richer macroinvertebrate assemblage
. 相似文献
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Cell growth and enzyme (alpha-amylase) production characteristics of Bacillus subtilis TN106 containing the recombinant plasmid pAT5 are investigated in batch and continuous cultures using a defined medium with glucose as the limiting nutrient. The batch culture studies demonstrate that the recombinant plasmid, reported earlier(1) to be stably maintained in the host, suffers from segregational and structural instabilities. The structural instability of this strain occurred during culture storage and can be eliminated in bioreactor experiments by using a modified inoculum preparation procedure. Such elimination allows an unbiased investigation of segregational instability via continuous culture studies. Such studies conducted with this fast growing microorganism, in the absence of antibiotic selection pressure, indicate a very efficient glucose utilization (very low residual glucose concentrations) over a wide range of dilution rates (0.16 h(-1) - 0.94 h(-1)). The nearly time-invariant and low residual glucose concentrations at each such dilution rate enable convenient estimation of growth parameters of the host and recombinant cells and frequency of segregational instability from transients in the resulting mixed cultures. The specific alpha-amylase activity exhibits an inverse relationship to the specific growth rate of recombinant cells. The growth of recombinant cells is not affected by the presence of antibiotic (kanamycin). The growth advantage of host cells over recombinant cells diminishes with increasing dilution rate. 相似文献
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Detection of low molecular mass GTP-binding proteins in chromaffin granules and other subcellular fractions of chromaffin cells 总被引:3,自引:0,他引:3
A homogenate of purified chromaffin cells was fractionated, after removal of the nuclear fraction, by sucrose density gradient ultracentrifugation. The presence and subcellular localization of low molecular mass GTP-binding proteins was explored by incubation of blots of proteins from different subcellular fractions with [alpha-32P]GTP in the presence of Mg2+. The fractions enriched in intact chromaffin granule markers, i.e. catecholamines, chromogranin A, chromogranin B and cytochrome b-561 were also enriched in labelled GTP-binding proteins. Two major labelled components of 23 and 29 kDa were rapidly detected by autoradiography. Traces of 26 and 27 kDa components were also present. These components were detectable in both plasma and granule membranes. In addition to these components, the cytosolic fraction contained another GTP-binding protein of about 20 kDa. Binding of [alpha-32P]GTP was specific and dependent on Mg2+. By analogy to the findings reported in non-mammalian systems, the observations described here suggest the involvement of low molecular mass GTP-binding proteins in the chromaffin cell secretory process. 相似文献