Akash Ranjan

Publications (25)87.27 Total impact

• Source

  Available from: PubMed Central

  Article: Prediction of DtxR regulon: identification of binding sites and operons controlled by Diphtheria toxin repressor in Corynebacterium diphtheriae.

  Sailu Yellaboina, Sarita Ranjan, Prachee Chakhaiyar, Seyed Ehtesham Hasnain, Akash Ranjan
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  ABSTRACT: The diphtheria toxin repressor, DtxR, of Corynebacterium diphtheriae has been shown to be an iron-activated transcription regulator that controls not only the expression of diphtheria toxin but also of iron uptake genes. This study aims to identify putative binding sites and operons controlled by DtxR to understand the role of DtxR in patho-physiology of Corynebacterium diphtheriae. Positional Shannon relative entropy method was used to build the DtxR-binding site recognition profile and the later was used to identify putative regulatory sites of DtxR within C. diphtheriae genome. In addition, DtxR-regulated operons were also identified taking into account the predicted DtxR regulatory sites and genome annotation. Few of the predicted motifs were experimentally validated by electrophoretic mobility shift assay. The analysis identifies motifs upstream to the novel iron-regulated genes that code for Formamidopyrimidine-DNA glycosylase (FpG), an enzyme involved in DNA-repair and starvation inducible DNA-binding protein (Dps) which is involved in iron storage and oxidative stress defense. In addition, we have found the DtxR motifs upstream to the genes that code for sortase which catalyzes anchoring of host-interacting proteins to the cell wall of pathogenic bacteria and the proteins of secretory system which could be involved in translocation of various iron-regulated virulence factors including diphtheria toxin. We have used an in silico approach to identify the putative binding sites and genes controlled by DtxR in Corynebacterium diphtheriae. Our analysis shows that DtxR could provide a molecular link between Fe+2-induced Fenton's reaction and protection of DNA from oxidative damage. DtxR-regulated Dps prevents lethal combination of Fe+2 and H2O2 and also protects DNA by nonspecific DNA-binding. In addition DtxR could play an important role in host interaction and virulence by regulating the levels of sortase, a potential vaccine candidate and proteins of secretory system.
  BMC Microbiology 10/2004; 4:38. · 3.04 Impact Factor
• Article: PredictRegulon: a web server for the prediction of the regulatory protein binding sites and operons in prokaryote genomes.

  Sailu Yellaboina, Jayashree Seshadri, M Senthil Kumar, Akash Ranjan
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  ABSTRACT: An interactive web server is developed for predicting the potential binding sites and its target operons for a given regulatory protein in prokaryotic genomes. The program allows users to submit known or experimentally determined binding sites of a regulatory protein as ungapped multiple sequence alignments. It analyses the upstream regions of all genes in a user-selected prokaryote genome and returns the potential binding sites along with the downstream co-regulated genes (operons). The known binding sites of a regulatory protein can also be used to identify its orthologue binding sites in phylogeneticaly related genomes where the trans-acting regulator protein and cognate cis-acting DNA sequences could be conserved. PredictRegulon can be freely accessed from a link on our world wide web server: http://www.cdfd.org.in/predictregulon/.
  Nucleic Acids Research 08/2004; 32(Web Server issue):W318-20. · 8.03 Impact Factor
• Article: Prediction of DtxR regulon: Identification of binding sites and operons controlled by Diphtheria toxin repressor in Corynebacterium diphtheriae

  Sailu Yellaboina, Sarita Ranjan, Prachee Chakhaiyar, Seyed Hasnain, Akash Ranjan
  [show abstract] [hide abstract]
  ABSTRACT: Abstract Background The diphtheria toxin repressor, DtxR, of Corynebacterium diphtheriae has been shown to be an iron-activated transcription regulator that controls not only the expression of diphtheria toxin but also of iron uptake genes. This study aims to identify putative binding sites and operons controlled by DtxR to understand the role of DtxR in patho-physiology of Corynebacterium diphtheriae . Result Positional Shannon relative entropy method was used to build the DtxR-binding site recognition profile and the later was used to identify putative regulatory sites of DtxR within C. diphtheriae genome. In addition, DtxR-regulated operons were also identified taking into account the predicted DtxR regulatory sites and genome annotation. Few of the predicted motifs were experimentally validated by electrophoretic mobility shift assay. The analysis identifies motifs upstream to the novel iron-regulated genes that code for Formamidopyrimidine-DNA glycosylase (FpG), an enzyme involved in DNA-repair and starvation inducible DNA-binding protein (Dps) which is involved in iron storage and oxidative stress defense. In addition, we have found the DtxR motifs upstream to the genes that code for sortase which catalyzes anchoring of host-interacting proteins to the cell wall of pathogenic bacteria and the proteins of secretory system which could be involved in translocation of various iron-regulated virulence factors including diphtheria toxin. Conclusions We have used an in silico approach to identify the putative binding sites and genes controlled by DtxR in Corynebacterium diphtheriae . Our analysis shows that DtxR could provide a molecular link between Fe⁺²-induced Fenton's reaction and protection of DNA from oxidative damage. DtxR-regulated Dps prevents lethal combination of Fe⁺²and H₂O₂and also protects DNA by nonspecific DNA-binding. In addition DtxR could play an important role in host interaction and virulence by regulating the levels of sortase, a potential vaccine candidate and proteins of secretory system.
  BMC Microbiology. 01/2004;
• Conference Proceeding: Computational prediction of DtxR regulon-A Dissection of physiological process controlled by DtxR in Corynebacterium species.

  Sailu Yellaboina, Prachee Chakhaiyar, Seyed Ehetsham Hasnain, Akash Ranjan
  2nd IEEE Computer Society Bioinformatics Conference (CSB 2003), 11-14 August 2003, Stanford, CA, USA; 01/2003
• Article: Influence of codon usage and translation initiation codon context in theAcNPV-based expression system: Computer analysis using homologous and heterologous genes

  Akash Ranjan, Seyed E. Hasnain
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  ABSTRACT: Codon usage by all the known gene sequences fromAutographa californica nuclear polyhedrosis virus (AcNPV) was compared with that of firefly luciferase (luc) and the beta subunit of human chorionic gonadotropin (hCG) expressed to contrasting levels in the baculovirus system. The highly expressedluc gene showed a codon usage similar toAcNPV genes, as reflected by a very low D-squared statistic value (0.78) and a similar G/C usage (45%) at wobble positions. However, the underexpressed hCG gene displayed a high D-squared value (7.3) and G/C usage (82.5%) at the wobble base positions. Alignment of the 20 nucleotides around the initiation codon of 23AcNPV genes identified a novel consensus translation initiation sequence aag/ta/tat/aa/cAAaATGaa/ct/ag/aAan, which was quite different from the Kozak consensus sequence (GCC)GCCA/GCCATGG. An extension of these analyses to a sample of other heterologous genes overexpressed and underexpressed in BEVS suggested similar trends. These theoretical analyses have important implications for heterologous gene expression in this system.
  Virus Genes 12/1994; 9(2):149-153. · 1.85 Impact Factor