The Mg-dependent salicylate synthase (MbtI) is a key enzyme involved in the biosynthesis of siderophores. Because iron is essential for the survival and pathogenicity of the microorganism, this protein constitutes an attractive target for antitubercular therapy, also considering the absence of homologous enzymes in mammals. An extension of the structure-activity relationships of our furan-based candidates allowed us to disclose the most potent competitive inhibitor known to date (, = 4 μM), which also proved effective on mycobacterial cultures. By structural studies, we characterized its unexpected Mg-independent binding mode. We also investigated the role of the Mg cofactor in catalysis, analyzing the first crystal structure of the MbtI-Mg-salicylate ternary complex. Overall, these results pave the way for the development of novel antituberculars through the rational design of improved MbtI inhibitors.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008425 | PMC |
| http://dx.doi.org/10.1021/acs.jmedchem.0c00373 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Omics-based Identification of the Broader Effects of 2-hydroxyisoflavanone Synthase Gene Editing on a Gene Regulatory Network Beyond Isoflavonoid Loss in Soybean Hairy Roots.
Plant Cell Physiol
December 2024
RIKEN Center for Sustainable Resource Science, Yokohama 230-0045, Japan.
Soybean (Glycine max) is a leguminous crop cultivated worldwide that accumulates high levels of isoflavones. Although previous research has often focused on increasing the soybean isoflavone content because of the estrogen-like activity of dietary soy in humans, the rapidly increasing demand for soybean as a plant-based meat substitute has raised concerns about excessive isoflavone intake. Therefore, the production of isoflavone-free soybean has been anticipated.
View Article and Find Full Text PDFPreeclampsia Treatment Aspirin/Clampsilin: Oxidative Stress, sFlt-1/PIGF Soluble Tyrosine Kinase 1, and Placental Growth Factor Monitoring.
Int J Mol Sci
December 2024
Department of Medical Chemistry and Biochemistry, Medical Faculty, Trakia University, 11 Armeiska Str., 6000 Stara Zagora, Bulgaria.
The present study aimed to investigate and compare oxidative stress biomarkers and antioxidant enzyme activity in the serum of women at risk of developing preeclampsia (PE) to prevent adverse pregnancy outcomes through early intervention. Changes in soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) levels were measured between 11 and 13 gestational weeks (gw.) before the onset of preeclampsia and its associated complications.
View Article and Find Full Text PDFThe transcription factor TGA2 orchestrates salicylic acid signal to regulate cold-induced proline accumulation in Citrus.
Plant Cell
December 2024
National Key Laboratory for Germplasm Innovation & Utilization of Horticultural Crops, College of Horticulture and Forestry Science, Huazhong Agricultural University, Wuhan 430070, China.
Plants subjected to cold stress have been observed to accumulate proline, but the underlying regulatory mechanism remains to be elucidated. In this study, we identified a pyrroline-5-carboxylate synthetase (P5CS)-encoding gene (CtrP5CS1) from trifoliate orange (Citrus trifoliata L.), a cold-hardy citrus species, as a critical gene for cold-induced proline accumulation.
View Article and Find Full Text PDFIsochorismate synthase is required for phylloquinone, but not salicylic acid biosynthesis in rice.
aBIOTECH
December 2024
State Key Laboratory of Plant Genomics, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101 China.
Article Synopsis
- Salicylic acid (SA) is a crucial plant hormone involved in growth and defense, produced mainly through two pathways: isochorismate synthase (ICS) and phenylalanine ammonia-lyase (PAL).
- Researchers used the CRISPR/Cas9 technology to create knockout mutants in rice that showed significant growth issues and lacked phylloquinone, suggesting a direct connection between OsICS and phylloquinone synthesis.
- Despite the growth defects, the levels of SA in the mutants remained unchanged, indicating that rice may utilize a different pathway for SA biosynthesis.
VOZ-dependent priming of salicylic acid-dependent defense against Rhizopus stolonifer by β-aminobutyric acid requires the TCP protein TCP2 in peach fruit.
Plant J
January 2025
Institute of Food Science, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, Zhejiang, P.R. China.
Vascular plant one-zinc finger (VOZ) transcription factors (TFs) play crucial roles in plant immunity. Nevertheless, how VOZs modulate defense signaling in response to elicitor-induced resistance is not fully understood. Here, the defense elicitor β-aminobutyric acid (BABA) resulted in the visible suppression of Rhizopus rot disease of peach fruit caused by Rhizopus stolonifer.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!