Publications by authors named "Santosh Panjikar"

Article Synopsis
  • Bacteria evolve mechanisms to optimize resource competition and adapt to new environments, specifically focusing on the import of isethionate by the sulfate-reducing bacterium Oleidesulfovibrio alaskensis.
  • This species uses a TRAP transporter (OaIsePQM) to facilitate isethionate import, with OaIseP binding the substrate and delivering it to the transporter for cellular uptake.
  • The study revealed the binding affinity of isethionate to OaIseP, provided structural insights into the protein’s conformation with and without the substrate, and suggests implications for antibiotic development targeting TRAP transporters.
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Tripartite ATP-independent periplasmic (TRAP) transporters are analogous to ABC transporters in that they use a substrate-binding protein to scavenge metabolites (e.g., N-acetylneuraminate) and deliver them to the membrane components for import.

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Article Synopsis
  • - PaaX is a transcriptional repressor involved in the degradation of phenylacetic acid (PAA) in bacteria, and it gets activated when phenylacetyl-coenzyme A (PA-CoA) binds to it, releasing it from its promoter sequences.
  • - The crystal structure of PaaX from E. coli reveals a unique dimeric formation made up of three distinct domains, including a winged helix-turn-helix domain and a dimerization domain resembling the Cas2 protein.
  • - Analysis of PaaX showed that its stability and solubility are influenced by ionic strength, and under certain conditions, it forms a stable intermediate that retains some structural features while exposing hydrophobic areas; these
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Chemokines are key regulators of leukocyte trafficking and attractive targets for anti-inflammatory therapy. Evasins are chemokine-binding proteins from tick saliva, whose application as anti-inflammatory therapeutics will require manipulation of their chemokine target selectivity. Here we describe subclass A3 evasins, which are unique to the tick genus Amblyomma and distinguished from "classical" class A1 evasins by an additional disulfide bond near the chemokine recognition interface.

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Previous studies demonstrated that ASP-3 was a novel calcium-binding protein from Arca subcrenata that effectively inhibited the proliferation of HepG2 cells. To further study the antitumor activity and mechanism of ASP-3, the cytotoxic effects of recombinant ASP-3 were evaluated in HepG2 cells. The results demonstrated that ASP-3 inhibited the proliferation of HepG2 cells by competitively binding to the EGF binding pocket of EGFR and inhibiting the JAK-STAT, RAS-RAF-MEK-ERK, and PI3K-Akt-mTOR signaling pathways mediated by EGFR.

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Herbicide resistance represents one of the biggest threats to our natural environment and agricultural sector. Thus, new herbicides are urgently needed to tackle the rise in herbicide-resistant weeds. Here, we employed a novel strategy to repurpose a 'failed' antibiotic into a new and target-specific herbicidal compound.

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Autotransporters (ATs) are a large family of bacterial secreted and outer membrane proteins that encompass a wide range of enzymatic activities frequently associated with pathogenic phenotypes. We present the structural and functional characterisation of a subtilase autotransporter, Ssp, from the opportunistic pathogen Serratia marcescens. Although the structures of subtilases have been well documented, this subtilisin-like protein is associated with a 248 residue β-helix and itself includes three finger-like protrusions around its active site involved in substrate interactions.

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CHD4 is an essential, widely conserved ATP-dependent translocase that is also a broad tumour dependency. In common with other SF2-family chromatin remodelling enzymes, it alters chromatin accessibility by repositioning histone octamers. Besides the helicase and adjacent tandem chromodomains and PHD domains, CHD4 features 1000 residues of N- and C-terminal sequence with unknown structure and function.

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The NtrC family of proteins senses external stimuli and accordingly stimulates stress and virulence pathways via activation of associated σ-dependent RNA polymerases. However, the structural determinants that mediate this activation are not well understood. Here, we establish using computational, structural, biochemical, and biophysical studies that MopR, an NtrC protein, harbors a dynamic bidirectional electrostatic network that connects the phenol pocket to two distal regions, namely the "G-hinge" and the "allosteric linker.

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The bacterial genus Mycobacterium includes important pathogens, most notably M. tuberculosis, which infects one-quarter of the entire human population, resulting in around 1.4 million deaths from tuberculosis each year.

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Strictosidine synthase (STR), the gate enzyme for monoterpenoid indole alkaloid biosynthesis, catalyzes the Pictet-Spengler reaction (PSR) of various tryptamine derivatives with secologanin assisted by "indole sandwich" stabilization. Continuous exploration with β-methyltryptamine (IPA) stereoselectively delivered the C6-methylstrictosidines and C6-methylvincosides by enzymatic and nonenzymatic PSR, respectively. Unexpectedly, the first "nonindole sandwich" binding mode was witnessed by the X-ray structures of STR1-ligand complexes.

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Graphene and graphene oxide have become the base of many advanced biosensors due to their exceptional characteristics. However, lack of some properties, such as inertness of graphene in organic solutions and non-electrical conductivity of graphene oxide, are their drawbacks in sensing applications. To compensate for these shortcomings, various methods of modifications have been developed to provide the appropriate properties required for biosensing.

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Article Synopsis
  • Weeds are becoming resistant to current herbicides, threatening agricultural production and creating a need for new herbicides with different mechanisms of action.
  • This study identified the first class of herbicides that inhibit dihydrodipicolinate synthase (DHDPS), a key enzyme in lysine biosynthesis, through a high-throughput chemical screening process.
  • The new inhibitors showed effectiveness in reducing seedling growth and germination, demonstrating their potential as pre-emergence herbicides to combat herbicide-resistant weeds.
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(Hp) is a human pathogen that lives in the gastric mucosa of approximately 50% of the world's population causing gastritis, peptic ulcers, and gastric cancer. An increase in resistance to current drugs has sparked the search for new Hp drug targets and therapeutics. One target is the disruption of nucleic acid production, which can be achieved by impeding the synthesis of 6-oxopurine nucleoside monophosphates, the precursors of DNA and RNA.

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Bacteria respond to environmental changes by inducing transcription of some genes and repressing others. Sialic acids, which coat human cell surfaces, are a nutrient source for pathogenic and commensal bacteria. The Escherichia coli GntR-type transcriptional repressor, NanR, regulates sialic acid metabolism, but the mechanism is unclear.

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Thioredoxin (TRX)-fold proteins are ubiquitous in nature. This redox scaffold has evolved to enable a variety of functions, including redox regulation, protein folding, and oxidative stress defense. In bacteria, the TRX-like disulfide bond (Dsb) family mediates the oxidative folding of multiple proteins required for fitness and pathogenic potential.

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Article Synopsis
  • Lysine biosynthesis in plants uses the diaminopimelate pathway, starting with the enzyme dihydrodipicolinate synthase (DHDPS), which is regulated by the end product, lysine.
  • In Arabidopsis thaliana, knockouts of two DHDPS isoforms show distinct phenotypes, even though they are over 85% identical in sequence.
  • The study found that AtDHDPS1 is significantly more sensitive to lysine than AtDHDPS2 due to subtle structural differences, particularly in a key residue, impacting its allosteric regulation and lysine dissociation.
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Article Synopsis
  • Plantacyclin B21AG is a circular bacteriocin from Lactiplantibacillus plantarum B21 that shows antimicrobial activity against harmful bacteria like Listeria and Clostridium.
  • The crystal structure of this 58-amino acid peptide was solved for the first time, revealing key features that contribute to its stability across various conditions.
  • Experiments demonstrated the significance of specific charged and aromatic amino acids for its antimicrobial effectiveness, with mutations leading to substantial reductions in activity, emphasizing their critical role in bacteriocin function.
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Exceptionally large crystals of posnjakite, CuSO(OH)(HO), formed during corrosion of a Swagelock(tm) Snubber copper gasket within the MX1 beamline at the ANSTO-Melbourne, Australian Synchrotron. The crystal structure was solved using synchrotron radiation to = 0.029 and revealed a structure based upon [Cu(OH)(HO)O] sheets, which contain Jahn-Teller-distorted Cu octa-hedra.

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Thiolases are a well characterized family of enzymes with two distinct categories: degradative, β-ketoadipyl-CoA thiolases and biosynthetic, acetoacetyl-CoA thiolases. Both classes share an identical catalytic triad but catalyze reactions in opposite directions. Moreover, it is established that in contrast to the biosynthetic thiolases the degradative thiolases can accept substrates with broad chain lengths.

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In environments where glucose is limited, some pathogenic bacteria metabolize host-derived sialic acid as a nutrient source. -Acetylmannosamine kinase (NanK) is the second enzyme of the bacterial sialic acid import and degradation pathway and adds phosphate to -acetylmannosamine using ATP to prime the molecule for future pathway reactions. Sequence alignments reveal that Gram-positive NanK enzymes belong to the Repressor, ORF, Kinase (ROK) family, but many lack the canonical Zn-binding motif expected for this function, and the sugar-binding EGH motif is altered to EGY.

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Article Synopsis
  • * Researchers are focusing on identifying new antibiotic targets, such as the enzyme dihydrodipicolinate synthase (DHDPS), vital for cell wall and protein synthesis in bacteria.
  • * This study uncovered mis-annotations in DHDPS genes of Acinetobacter baumannii and Klebsiella pneumoniae, confirming them through enzyme kinetics and X-ray crystallography, emphasizing the need for accurate gene annotation in key pathogens.
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Pseudomonas aeruginosa is one of the leading causes of nosocomial infections, accounting for 10% of all hospital-acquired infections. Current antibiotics against P. aeruginosa are becoming increasingly ineffective due to the exponential rise in drug resistance.

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Two commonly encountered bottlenecks in the structure determination of a protein by X-ray crystallography are screening for conditions that give high-quality crystals and, in the case of novel structures, finding derivatization conditions for experimental phasing. In this study, the phasing molecule 5-amino-2,4,6-triiodoisophthalic acid (I3C) was added to a random microseed matrix screen to generate high-quality crystals derivatized with I3C in a single optimization experiment. I3C, often referred to as the magic triangle, contains an aromatic ring scaffold with three bound I atoms.

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Article Synopsis
  • Autotransporters are a major group of proteins in Gram-negative bacteria, primarily involved in helping these bacteria attach to host surfaces.
  • The study details the structure of UpaB, a specific autotransporter found in uropathogenic E. coli, and shows its ability to interact with important host molecules, glycosaminoglycans, and fibronectin.
  • The research uncovers unexpected diversity in the structure of autotransporters, suggesting they may have more complex roles in bacterial interactions with hosts during infections.
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