Biomedical subjects

Sarita Ranjan

Publications and source records attributed to Sarita Ranjan.

6 recordsLinked to original sources

PubMed2006

In silico analysis and characterization of GntR family of regulators from Mycobacterium tuberculosis.

The genome of Mycobacterium tuberculosis contains a large number of hypothetical and poorly characterized proteins including the proteins belonging to the GntR family. The regulators of this family show a conserved N-terminal DNA-binding domain but have a highly diverse C-terminal domain involved in the effector-binding and/or oligomerization. This heterogeneity has led to a further classification of this family into various subfamilies. The sequence analysis of the M. tuberculosis genome revealed that five genes encode for FadR-like regulators, one gene for HutC-like regulator and one for YtrA-like regulator. This classification was also consistent with specific secondary structural features known to be associated with FadR, HutC and YtrA subfamilies. Out of the five FadR-like regulators three of the regulators were further subclassified into FadR group and two of them into the VanR group. Interestingly Rv3060c, a FadR-like regulator, was shown to have an unusual size which led us to demonstrate it as a product of a gene duplication and fusion event. Thus this study extends the genome annotation of M. tuberculosis and provides important leads for initiating experimental characterization of these proteins, which in turn will enrich our knowledge of their role in cellular physiology.

Bacterial Proteins↗

PubMed2006

iCR: a web tool to identify conserved targets of a regulatory protein across the multiple related prokaryotic species.

Gene regulatory circuits are often commonly shared between two closely related organisms. Our web tool iCR (identify Conserved target of a Regulon) makes use of this fact and identify conserved targets of a regulatory protein. iCR is a special refined extension of our previous tool PredictRegulon- that predicts genome wide, the potential binding sites and target operons of a regulatory protein in a single user selected genome. Like PredictRegulon, the iCR accepts known binding sites of a regulatory protein as ungapped multiple sequence alignment and provides the potential binding sites. However important differences are that the user can select more than one genome at a time and the output reports the genes that are common in two or more species. In order to achieve this, iCR makes use of Cluster of Orthologous Group (COG) indices for the genes. This tool analyses the upstream region of all user-selected prokaryote genome and gives the output based on conservation target orthologs. iCR also reports the Functional class codes based on COG classification for the encoded proteins of downstream genes which helps user understand the nature of the co-regulated genes at the result page itself. iCR is freely accessible at http://www.cdfd.org.in/icr/.

Bacterial Proteins↗

PubMed2006

Comparative analysis of iron regulated genes in mycobacteria.

Iron dependent regulator, IdeR, regulates the expression of genes in response to intracellular iron levels in M. tuberculosis. Orthologs of IdeR are present in all the sequenced genomes of mycobacteria. We have used a computational approach to identify conserved IdeR regulated genes across the mycobacteria and the genes that are specific to each of the mycobacteria. Novel iron regulated genes that code for a predicted 4-hydroxy benzoyl coA hydrolase (Rv1847) and a protease dependent antibiotic regulatory system (Rv1846c, Rv0185c) are conserved across the mycobacteria. Although Mycobacterium natural-resistance-associated macrophage protein (Mramp) is present in all mycobacteria, it is, as predicted, an iron-regulated gene in only one species, M. avium subsp. paratuberculosis. We also observed an additional iron-regulated exochelin biosynthetic operon, which is present only in non-pathogenic Mycobacterium, M. smegmatis.

Amino Acid Sequence↗

PubMed2006

IdeR in mycobacteria: from target recognition to physiological function.

In mycobacteria, iron dependent transcription regulator (IdeR) regulates transcription of genes in response to iron levels. The IdeR regulated genes have been investigated mostly in M. tuberculosis, M. smegmatis, and in few of the other related species. Recent advances in crystal structure solution and computational as well as experimental identification of IdeR targets has provided insight into IdeR structure and function. Here in this review we take stock of current state of knowledge on IdeR and its targets to understand the underlying design of the IdeR regulon and its role in mycobacterial physiology.

Bacterial Proteins↗

PubMed2005

Plasmodium falciparum: genetic diversity of C-terminal region of MSP-1 in isolates from Indian sub-continent.

Malaria parasites exhibit sequence diversity for a number of stage specific antigens. Several studies have proved that merozoite surface protein-1 (MSP-1) is an effective target eliciting a protective immune response. The MSP-1(42) region comprising two EGF-like domains is involved in generating protective immune response in humans and other experimental animals. Searching for point mutations in this region is essential in view of vaccine development. We have investigated the sequence variations in Plasmodium falciparum MSP-1 carboxy terminal region in field isolates from different regions in India. Our study reveals the presence of eight variant types of MSP-1(19) in the Indian sub-continent, which comprise of E-TSR-L, Q-TSR-L, E-TSG-L, Q-KNG-L, Q-KNG-F, E-KNG-L, E-KNG-F, and E-KYG-F. The last named allele is a novel variant being reported for the first time.

Alleles↗

PubMed2004

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

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+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.

Bacterial Proteins↗