Modulation of intracellular guanosine 3′,5′‐bispyrophosphate ((p)ppGpp) level, the effector of the stringent response, is crucial for survival as well as optimal growth of prokaryotes and, thus, for bacterial pathogenesis and dormancy. In Mycobacterium tuberculosis (Mtb), (p)ppGpp synthesis and degradation are carried out by the bifunctional enzyme MtRel, which consists of 738 residues, including an N‐terminal hydrolase‐ and synthetase‐domain (N‐terminal domain or NTD) and a C‐terminus with a ribosome‐binding site. Here, we present the first crystallographic structure of the enzymatically active MtRel NTD determined at 3.7 Å resolution. The structure provides insights into the residues of MtRel NTD responsible for nucleotide binding. Small‐angle X‐ray scattering experiments were performed to investigate the dimeric state of the MtRel NTD and possible substrate‐dependent structural alterations.
Abstract:Neisseria meningitidis is a parasitic gram-negative bacterium of the family Neisseriaceae (Proteobacteria) and it causes many human diseases including meningitidis and septicemia. One of its strains, H44/76, has natural transformation capacity, thus it is important to identify possible novel drug targets and to develop serogroup B vaccines against this opportunist pathogen. In the complete genome of N. meningitidis strain H44/76, there are 1961 coding genes out of which 544 encodes for hypothetical proteins (HPs). Due to their less homology and relatedness to other known proteins, HPs may serve as potential drug targets. We performed extensive functional analysis of these HPs with the help of Bioinformatics tools and assigned functions to 235 HPs, out of which 202 were annotated with high confidence whereas 33 with less confidence. In this study, we have used a combination of latest tools to acquire information about the conserved regions, families, pathways, interactions, localization and virulence related to a particular protein. We also categorized these proteins as transporters, regulators, enzymes, binding proteins, virulent proteins. The outcome of this intensive study may help in the comprehensive understanding of pathogenesis, drug resistance, adaptability to host, epidemic causes and drug discovery for treatment of the diseases.
The stringent response (SR) is crucial for survival as well as optimal growth of Mycobacterium tuberculosis (Mtb). Mycobacterial cells initiate SR during nutrient and energy limitations by increasing levels of (p)ppGpp. In Mtb, (p)ppGpp synthesis and degradation are carried out by the bifunctional enzyme Rel. Here, we present the dimeric solution structure of its ACT domain, unraveled its specific binding to valine, and determined the critical residues in Val‐ACT binding.
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Coronavirus diseases (COVID-19) is caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), which is a
positive single-stranded RNA virus having a large genome ~30 kb. SARS-CoV-2 is zoonotic and highly contagious, causing severe
pneumonia-like symptoms. The efficacy of the different potential drug and drug candidates against COVID-19 has been investigated which
are under various stages of clinical trials. The drugs effective against SARS, and Middle east respiratory syndrome (MERS), have been
proposed to have a high potential for the treatment of COVID-19. Here, we selected plant-based materials implicated in the prevention and
therapy of COVID-19. The vaccine has shown impressive results in producing antibodies against SARS-CoV2 and has been evaluated for
safety, tolerance, and preliminary immunogenicity. Similarly, DNA/RNA-based therapy shown high clinical significance. The plant produces
secondary metabolites in response to viral infection to protect them. Many nanomaterials produced by carbohydrates and lipids been exploited
for their in-vitro and in-vivo delivery of antiviral therapeutics. Different classes of secondary metabolites have a different mechanism to
counter virus attacks. While some natural medicines in the form of vitamins, minerals, herbs, and other nutrients help to enhance immunity,
such measures should not replace social distancing, quarantining special care to protect from COVID-19. The standards of reporting were in
accordance with the PRISMA guidelines.
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