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Molecular machines manage the flow of genetic information in DNA to active and functional proteins through the process of central dogma. The machines that mediate the information transfer from DNA to protein are RNA polymerase and ribosome. The synthesis of RNA from a DNA template is catalysed by RNA polymerase and the process is known as transcription. On the other hand, the process of information transfer from RNA to protein is mediated by ribosome. Our laboratory, since several decades has been working on the mechanistic details of transcription process in bacteria under stress.

The Lab focusses on the following questions:

  • Under nutritional starvation bacteria elicit 'stringent response' with concomitant synthesis of alarmone like (p)ppGpp. We focus our attention on how ppGpp modulate differential gene expression to balance the efficient utilization of available energy within the cell.
  • The second messenger like c-di-GMP or c-di-AMP play major role in bacterial communication network known as Quorum sensing. The proximate aim of our lab is to monitor the cross talk between stringent response and Quorum sensing.
  • RNA polymerase is a multi-subunit enzyme and every subunit is essential except omega, which can be deleted without any deleterious effect. However, omega plays a major role in maturation of the enzyme and maintaining its structural integrity. We are trying to find out through critical genetic experiments, the structure-function relationship in omega.
  • Lastly, we devote our time to characterise yet another protein Dps, which is the iron store house in bacteria and is synthesized under stress like starvation.


Recent Publications

A Mutation Directs the Structural Switch of DNA Binding Proteins under Starvation to a Ferritin-like Protein Cage

Structre

Proteins of the ferritin family are ubiquitous in living organisms. With their spherical cage-like structures they are the iron storehouses in cells. Subfamilies of ferritins include 24-meric ferritins and bacterioferritins (maxiferritins), and 12-meric Dps (miniferritins). Dps safeguards DNA by direct binding, affording physical protection and safeguards from free radical-mediated damage by sequestering iron in its core. The maxiferritins can oxidize and store iron but cannot bind DNA. Here we show that a mutation at a critical interface in Dps alters its assembly from the canonical 12-mer to a ferritin-like 24-mer under crystallization. This structural switch was attributed to the conformational alteration of a highly conserved helical loop and rearrangement of the C-terminus. Our results demonstrate a novel concept of mutational switch between related protein subfamilies and corroborate the popular model for evolution by which subtle substitutions in an amino acid sequence lead to diversification among proteins.

Synthetic Arabinomannan Heptasaccharide Glycolipids Inhibit Biofilm Growth and Supplements Isoniazid Effects in Mycobacterium smegmatis

ChemBioChem

Biofilm formation, involving attachment to an adherent surface, is a critical survival strategy of mycobacterial colonies in hostile environmental conditions. Here we report the synthesis of heptasaccharide glycolipids based on mannopyranoside units anchored on to a branched arabinofuranoside core. Two types of glycolipids?2,3-branched and 2,5-branched?were synthesized and evaluated for their efficacies in inhibiting biofilm growth by the non-pathogenic mycobacterium variant Mycobacterium smegmatis. Biofilm formation was inhibited at a minimum biofilm growth inhibition concentration (MBIC) of 100??g?mL?1 in the case of the 2,5-branched heptasaccharide glycolipid. Further, we were able to ascertain that a combination of the drug isoniazid with the branched heptasaccharide glycolipid (50??g?mL?1) potentiates the drug, making it three times more effective, with an improved MBIC of 30??g?mL?1. These studies establish that synthetic glycolipids not only act as inhibitors of biofilm growth, but also provide a synergistic effect when combined with significantly lowered concentrations of isoniazid to disrupt the biofilm structures of the mycobacteria.

Two zinc finger proteins from Mycobacterium smegmatis: DNA binding and activation of transcription.

Genes to Cells

Single zinc finger domain containing proteins are very few in number. Of numerous zinc finger proteins in eukaryotes, only three of them like GAGA, Superman and DNA binding by one finger (Dof) have single zinc finger domain. Although few zinc finger proteins have been described in eubacteria, no protein with single C4 zinc finger has been described in details in anyone of them. In this article, we are describing two novel C-terminal C4 zinc finger proteins—Msmeg_0118 and Msmeg_3613 from Mycobacterium smegmatis. We have named these proteins as Mszfp1 (Mycobacterial Single Zinc Finger Protein 1) and Mszfp2 (Mycobacterial Single Zinc Finger Protein 2). Both the proteins are expressed constitutively, can bind to DNA and regulate transcription. It appears that Mszfp1 and Mszfp2 may activate transcription by interacting with RNA polymerase.

Pup recycling regulates the proteasome.

The FEBS Journal

The Pup proteasome system (PPS) in bacteria is equivalent to the eukaryotic ubiquitin proteasome system (UPS) that allows controlled protein degradation. Unlike the UPS, however, the PPS machinery and regulation is still poorly understood. In this issue of The FEBS Journal, Gur and colleagues combine experimental and modelling analyses to show how the PPS maintains steady-state levels of protein pupylation and consequently tightly controlled protein degradation.