Background: KATmt is the first identified cAMP-regulated protein lysine acetylase in mycobacteria. Results: KATmt acylates fatty acyl CoA ligases in vivo in a cAMP-dependent manner, thus regulating their activity. Conclusion: Mycobacteria utilize KATmt to regulate the metabolic pool of acetyl and propionyl CoA. Significance: We provide novel paradigms for linking cAMP signaling and fatty acid metabolism in mycobacteria.
Background: Histidine 69 in the propeptide is a pH sensor that mediates compartment-specific furin activation. Results: Histidine 69 protonation exposes the activation loop for proteolysis only within an optimal window for pH-dependent activation. Conclusion: A small structural change functions as the trigger that regulates precise spatiotemporal activation of furin. Significance: Our work provides insights into how individual proprotein convertases encode their unique compartmentspecific activation.
Antidepressants induce structural remodeling in the adult hippocampus, including changes in dendritic arbors, axonal sprouting, neurogenesis, and endothelial cell proliferation. Such forms of structural plasticity take place in the context of the extracellular matrix environment and are known to be regulated by matrix metalloproteinases (MMPs), in particular MMP-2/9, and their endogenous regulators, the tissue inhibitors of the metalloproteinases (TIMPs 1-4). Given the hippocampal structural remodeling associated with antidepressant treatments, we hypothesized that antidepressants may regulate the expression and activity of MMP-2/9 and TIMPs 1-4. The influence of distinct classes of antidepressants, namely, electroconvulsive seizure, fluoxetine, tranylcypromine, and desipramine, on the gene expression of MMP-2, MMP-9, and TIMPs 1-4 in the hippocampus was determined using radioactive in situ hybridization. In addition, zymography studies addressed the regulation of the gelatinase activity of MMP-2/9 following acute and chronic antidepressant administration. We observed that acute and chronic ECS differentially regulate the transcript levels of MMP-2/9 and TIMPs 1-4 and also increase gelatinase activity in the hippocampus. Acute and chronic pharmacological antidepressants on the other hand differentially alter the expression of the TIMPs without any observed effect on hippocampal MMP-2/9 expression or activity. These findings raise the possibility that extracellular matrix modifying enzymes and their endogenous regulators may serve as targets for antidepressant treatments and suggests the possibility that they may contribute to antidepressant-mediated structural plasticity in the hippocampus.
We have determined the non-synonymous Single-Nucleotide Polymorphisms (nsSNPs) of PLD2 gene and its variations in different populations to understand its role in hypertension. Out of 350 SNPs, six are found to be non-synonymous, of which two showed significant damaging effect and SNP variability with large differences among the Minor Allele Frequency (MAF) observed in various populations. The amino acid change found for rs2286672 is from arginine to cysteine, i.e., from largest amino acid containing guanidino group to a small amino acid containing sulfhydryl group, and for rs3764897, it is from glycine to serine, i.e., from a hydrophobic amino acid to a hydrophilic amino acid. Hence, owing to the complete change in side chains and polarity of the amino acid residues brought about by these SNPs, the structure of the protein might be altered and hence the function might be affected, leading to dysregulation of blood pressure.
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