Sang-Kee Song , Dong Won Jeong , Yun Ju Kim , John Schiefelbein , Myeong Min Lee
{"title":"Negative feedback regulation of GLABRA1 contributes to epidermal cell patterning in the Arabidopsis root","authors":"Sang-Kee Song , Dong Won Jeong , Yun Ju Kim , John Schiefelbein , Myeong Min Lee","doi":"10.1016/j.bbrc.2024.150869","DOIUrl":"10.1016/j.bbrc.2024.150869","url":null,"abstract":"<div><div><em>GLABRA1</em> (<em>GL1</em>), which encodes an R2R3 MYB transcription factor, is a key regulator of trichome patterning in the aerial organs of Arabidopsis (<em>Arabidopsis thaliana</em>). Although it has been generally assumed that <em>GL1</em> functions exclusively in shoots and is not expressed in roots, reverse transcription polymerase chain reaction (RT-PCR) analysis has revealed that <em>GL1</em> is indeed expressed in roots. To investigate whether <em>GL1</em> plays a role in root epidermal patterning, we analyzed the effects of <em>gl1</em> mutations in sensitized genetic backgrounds. Our findings show that <em>gl1</em> mutants enhance the root epidermal phenotype of a weak allele of the <em>werewolf</em> (<em>wer</em>) mutant and suppress the phenotype of the <em>caprice</em> (<em>cpc</em>) mutant. We also demonstrate that the <em>GL1</em> promoter is active in N-position epidermal cells, and that the GFP-GL1 fusion protein is predominantly localized in the nucleus of N-position cells. Furthermore, we provide evidence that <em>GL1</em> expression is positively regulated by <em>WER</em>, <em>GLABRA3</em>, <em>ENHANCER OF GLABRA3</em>, and <em>TRANSPARENT TESTA GLABRA1</em>, while negatively regulated by <em>CPC</em>, <em>TRIPTYCHON</em>, and <em>GLABRA2</em> (<em>GL2</em>). Notably, <em>GL2</em>, which is positively regulated by GL1, moderately represses <em>GL1</em> expression, and both <em>GL1</em> and <em>GL2</em> are positively regulated by <em>WER</em> in N-position cells. These findings suggest that a negative feedback regulation of <em>GL1</em> expression via GL2 contributes to the fine-tuning of non-hair cell fate determination in Arabidopsis root epidermis.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lubos Cipak , Barbara Sivakova , Jana Bellova , Maksym Danchenko , Jan Jurcik , Ingrid Cipakova , Laura Olivia Lalakova , Juraj Gregan , Peter Barath
{"title":"Characterization of Ksg1 protein kinase-dependent phosphoproteome in the fission yeast S. pombe","authors":"Lubos Cipak , Barbara Sivakova , Jana Bellova , Maksym Danchenko , Jan Jurcik , Ingrid Cipakova , Laura Olivia Lalakova , Juraj Gregan , Peter Barath","doi":"10.1016/j.bbrc.2024.150895","DOIUrl":"10.1016/j.bbrc.2024.150895","url":null,"abstract":"<div><div>Ksg1 is an essential protein kinase of the fission yeast <em>S. pombe</em> that belongs to the AGC kinase family and is homologous to the mammalian PDPK1 kinase. Previous studies have shown that Ksg1 functions in the nutrient-sensing TOR signaling pathway and is involved in the phosphorylation and activation of other AGC kinases, thereby affecting various downstream targets related to metabolism, cell division, stress response, and gene expression. To date, the molecular function of Ksg1 has been analyzed using its temperature sensitive mutants or mutants expressing its truncated isoforms, which are not always suitable for functional studies of Ksg1 and the identification of its targets. To overcome these limitations, we employed a chemical genetic strategy and used a conditional <em>ksg1</em><sup><em>as</em></sup> mutant sensitive to an ATP analog. Combining this mutant with quantitative phosphoproteomics analysis, we identified 1986 phosphosites that were differentially phosphorylated when Ksg1<sup><em>as</em></sup> kinase was inhibited by an ATP analog. We found that proteins whose phosphorylation was dysregulated after inhibition of Ksg1<sup><em>as</em></sup> kinase were mainly represented by those involved in the regulation of cytokinesis, contractile ring contraction, cell division, septation initiation signaling cascade, intracellular protein kinase cascade, barrier septum formation, protein phosphorylation, intracellular signal transduction, cytoskeleton organization, cellular response to stimulus, or in RNA, ncRNA and rRNA processing. Importantly, proteins with significantly down-regulated phosphorylation were specifically enriched for R-<em>X</em>-<em>X</em>-S and R-<em>X</em>-R-<em>X</em>-<em>X</em>-S motifs, which are typical consensus substrate sequences for phosphorylation by the AGC family of kinases. The results of this study provide a basis for further analysis of the role of the Ksg1 kinase and its targets in <em>S. pombe</em> and may also be useful for studying Ksg1 orthologs in other organisms.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jun Lei , Jingli Chen , Jian Chen , Jialing Fang , Zihao Zhou , Aifang Xu
{"title":"Epigallocatechin-3-gallate induces immunogenic cell death and enhances cancer immunotherapy in colorectal cancer","authors":"Jun Lei , Jingli Chen , Jian Chen , Jialing Fang , Zihao Zhou , Aifang Xu","doi":"10.1016/j.bbrc.2024.150907","DOIUrl":"10.1016/j.bbrc.2024.150907","url":null,"abstract":"<div><div>The induction of immunogenic cell death (ICD) can activate antitumor immune response to potentiate cancer immunotherapy. In this study, we observed the antitumor activity following combinatorial therapy with anti-CTLA4 antibody and epigallocatechin-3-gallate (EGCG) in CT26 tumors.Indeed, EGCG triggered colon cancer cells ICD with the secretion of high-mobility group protein B1 (HMGB1) and the surface expression of calreticulin (CRT) and heat shock protein 70 (HSP70). Mice treated with EGCG promoted the maturation of dendritic cells and enhanced the effector function of CD8<sup>+</sup> T cells within tumors to remodel the tumor immune microenvironment. Overall, these results indicate that EGCG, a novel ICD inducer, triggers ICD in CRC, and provides a new concept for cancer immunotherapy.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shweta Singh , Priyanka Gopi , Palak Sharma , Majji Sai Sudha Rani , Prateek Pandya , Mohd Sajid Ali
{"title":"Hemoglobin targeting potential of aminocarb pesticide: Investigation into dynamics, conformational stability, and energetics in solvent environment","authors":"Shweta Singh , Priyanka Gopi , Palak Sharma , Majji Sai Sudha Rani , Prateek Pandya , Mohd Sajid Ali","doi":"10.1016/j.bbrc.2024.150896","DOIUrl":"10.1016/j.bbrc.2024.150896","url":null,"abstract":"<div><div>Aminocarb (AMC), a carbamate pesticide, due to its prevalent usage exhibits increased accumulation in the environment affecting both insects and humans. It enters the human body via food grains and be transported through bloodstream. AMC's chemical structure, containing specific molecular frameworks and functional groups, enables it to bind with proteins like albumin and hemoglobin. Given that molecules with similar architecture are known to bind with hemoglobin, we aimed to explore Aminocarb's binding capability and the potential mechanism or mode of its interaction with hemoglobin. Hb being a tetramer with a profound interface between amino acid chains offers multiple binding sites. It is therefore important to investigate the structural aspects of binding of AMC by employing various spectroscopic and in-silico methods. The surface of the α1 chain near the α1β2 interface emerges as the preferred binding site for AMC, primarily due to its conformational restrictions. In its bound state, AMC tends to maintain a relaxed conformation, closely resembling its globally optimized geometry, and resides in close proximity to the α1 chain via multiple hydrophobic contacts and water bridge as observed in molecular dynamics (MD) simulations. Fluorescence quenching experiments showed moderate binding strength (7.7 × 10⁴ L M⁻<sup>1</sup> at 288 K, 7.8 × 10⁴ L M⁻<sup>1</sup> at 298 K, 7.9 × 10⁴ L M⁻<sup>1</sup> at 308 K) and spontaneous binding, driven by hydrophobic and van der Waals interactions, as indicated by enthalpy (0.80–0.91 kJ mol⁻<sup>1</sup>), entropy (0.0970–0.0974 kJ mol⁻<sup>1</sup>), and Gibbs free energy (−27.13 to - 29.08 kJ mol⁻<sup>1</sup>). Circular dichroism experiments reveal no major structural changes in Hb. Quantum chemical calculations and MD simulations reveal conformation-dependent energy differences, enhancing our understanding of AMC's binding mechanism to Hb.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Triple-regulated conditionally replicating adenovirus for effective and safer treatment of peritoneal carcinomatosis","authors":"Junichi Kamizono , Yuya Nishikawaji , Satoshi Nagano , Minako Ikeda , Yoshiharu Horikawa , Taro Kamisasanuki , Kaoru Mitsui , Eriko Matsuda , Ken-ichiro Kosai","doi":"10.1016/j.bbrc.2024.150894","DOIUrl":"10.1016/j.bbrc.2024.150894","url":null,"abstract":"<div><div>There is no effective therapy for peritoneal carcinomatosis derived from gastric cancer. An ideal conditionally replicating adenovirus (CRA) that selectively replicates in and kills cancer cells has not been developed for gastric cancer-derived peritoneal carcinomatosis. Using our platform technology of CRA regulated and treating tumors with multiple factors (m-CRA), we generated two types of survivin-responsive m-CRAs, Surv.m-CRA-CMVp and Surv.m-CRA-CEAp, consisting of E1A downstream of the survivin promoter, and the mutated E1B gene downstream of the human cytomegalovirus immediate early gene enhancer/promoter and carcinoembryonic antigen promoter, respectively. Survivin mRNA was expressed at high and undetectable levels in two gastric cancer cells and eleven normal cells, respectively. Carcinoembryonic antigen was expressed at high and very low levels in MKN-45 gastric cancer and normal PrEC cells, respectively, and was not detected in other cell types. While both Surv.m-CRA-CEAp and Surv.m-CRA-CMVp exhibited potent cytotoxic effects on MKN-45 cells <em>in vitro</em>, Surv.m-CRA-CEAp significantly reduced cytotoxicity to normal cells compared to Surv.m-CRA-CMVp. Control mice that received an intraperitoneal injection of MKN-45 cells gradually lost body weight and died of peritoneal carcinomatosis within 98 days. In contrast, all mice receiving Surv.m-CRA-CEAp or Surv.m-CRA-CMVp-infected MKN-45 cells increased their body weight and survived 120 days. In conclusion, the triple-regulated Surv.m-CRA-CEAp enhances cancer specificity (<em>i.e.</em>, safety) without reducing the potent therapeutic effect for carcinoembryonic antigen-positive gastric cancer-derived peritoneal carcinomatosis. The modified E1B promoter strategy of CRA facilitates the development of novel CRAs for the effective and safe treatment of a variety of refractory cancers.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142553927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nani Yang , Tianqing Yu , Beiyao Zheng , Wentao Sun , Yue Li , Wei Zhang , Yuanyuan Chen , Li Yuan , Xue Jun Wang , Junbin Wang , Fen Yang
{"title":"POSTN promotes the progression of NSCLC via regulating TNFAIP6 expression","authors":"Nani Yang , Tianqing Yu , Beiyao Zheng , Wentao Sun , Yue Li , Wei Zhang , Yuanyuan Chen , Li Yuan , Xue Jun Wang , Junbin Wang , Fen Yang","doi":"10.1016/j.bbrc.2024.150891","DOIUrl":"10.1016/j.bbrc.2024.150891","url":null,"abstract":"<div><div>Aberrant upregulation of Periostin (POSTN) expression has been implicated in various disease-related pathological cascades, notably inflammatory responses, fibrotic processes and tumor progression, including non-small cell lung cancer (NSCLC). The present study aimed to elucidate the functional role and underlying mechanisms of POSTN in NSCLC. Immunohistochemical and Western blot analysis consistently revealed elevated POSTN levels in NSCLC tissues and cell lines. POSTN expression negatively correlated with patient prognosis. Functional experiments utilizing POSTN-targeting siRNAs demonstrated a significant suppression of NSCLC cell proliferation, epithelial-to-mesenchymal transition (EMT), migration and invasion, whereas POSTN overexpression via plasmid transfection enhanced these oncogenic properties. Mechanistically, RNA sequencing analysis and subsequent validation studies revealed that POSTN positively modulates the transcriptional expression of tumor necrosis factor alpha-induced protein 6 (TNFAIP6) in NSCLC. Notably, a positive correlation was observed between POSTN and TNFAIP6 expression levels, and their overexpression positively correlated with NSCLC progression. Furthermore, TNFAIP6 overexpression rescued the inhibitory effects of POSTN knockdown on NSCLC malignant phenotypes. Collectively, our findings indicate that POSTN promotes NSCLC malignancy through TNFAIP6 upregulation, positioning POSTN as a promising biomarker and potential therapeutic target for NSCLC prognosis and treatment strategies in clinical settings.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"ZBTB7A as a therapeutic target for cancer","authors":"Ying Zhou , Xisha Chen , Xuyu Zu","doi":"10.1016/j.bbrc.2024.150888","DOIUrl":"10.1016/j.bbrc.2024.150888","url":null,"abstract":"<div><div>ZBTB7A, alternatively referred to Pokemon, FBI-1, LRF, and OCZF, is classified as a member of POK/ZBTB protein family of transcriptional repressors. ZBTB7A binds to targeted DNA via C-terminal zinc fingers and recruits co-compression complexes through N-terminal BTB ⁄ POZ domain to impede transcription. ZBTB7A regulates a range of fundamental biological processes such as cell proliferation, differentiation and apoptosis, B- and T-lymphocyte fate determination and thymic insulin expression and self-tolerance. Accumulating evidence has demonstrated an important role of ZBTB7A in the initiation and advancement of tumors, thus making ZBTB7A emerge as an appealing target. This review examines the functions and regulatory mechanisms of ZBTB7A in a range of common solid tumors, including hepatocellular carcinoma, breast cancer, prostate cancer and lung cancer, as well as hematological malignancies. Notably, the review concludes with a summary of the recent applications of targeting ZBTB7A in clinical treatments through gene silencing, immunotherapy and chemotherapeutic approaches to halt or slow tumor progression. We focus on the functional role and regulatory mechanisms of ZBTB7A in cancer with the goal of providing new insights for the development of more effective cancer therapeutic strategies.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142534777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hiroe Go , Nam Ji Sung , Jaeil Choi , Lila Kim , Eun Jung Park
{"title":"6′-sialyllactose prevents dexamethasone-induced muscle atrophy by controlling the muscle protein degradation pathway","authors":"Hiroe Go , Nam Ji Sung , Jaeil Choi , Lila Kim , Eun Jung Park","doi":"10.1016/j.bbrc.2024.150892","DOIUrl":"10.1016/j.bbrc.2024.150892","url":null,"abstract":"<div><div>Sarcopenia is associated with various geriatric diseases, such as gait disorders, falls, malnutrition, and osteoporosis. Accordingly, interest in the prevention and treatment of sarcopenia has grown over the years. The human milk oligosaccharide (HMO) 6′-sialyllactose (6′-SL) is known to improve exercise performance, reduce muscle fatigue, and improve GNE myopathy; however, its effect on sarcopenia has not yet been reported. In this study, we aimed to investigate the efficacy of 6′-SL in dexamethasone-induced muscle atrophy, which is a widely used model for the study of sarcopenia. The effects of 6′-SL on differentiated C2C12 skeletal muscle cells and on mice were examined by treatment with 6′-SL in the presence or absence of dexamethasone. 6′-SL was found to inhibit the dexamethasone-induced decrease of MHC expression, as well as to prevent reduction in the number, length, and width of myotubes. Furthermore, the dexamethasone-induced upregulation of myostatin, muscle RING-finger protein-1 (MuRF1), and atrogin-1 were also inhibited by 6′-SL treatment. In mice, intraperitoneal administration of dexamethasone caused decreases in muscle fiber diameter, muscle weight, and exercise performance, most of which were significantly inhibited by oral treatment with 6′-SL. Therefore, utilization of 6′-SL could contribute to the prevention and treatment of muscle atrophy and sarcopenia.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D.L. Falkoski , S.T. de Rezende , V.M. Guimarães , M.V. de Queiroz , M.N. Almeida
{"title":"Purification and characterization of α-galactosidases from Penicillium griseoroseum for efficient soymilk hydrolysis","authors":"D.L. Falkoski , S.T. de Rezende , V.M. Guimarães , M.V. de Queiroz , M.N. Almeida","doi":"10.1016/j.bbrc.2024.150905","DOIUrl":"10.1016/j.bbrc.2024.150905","url":null,"abstract":"<div><div>Soybean utilization is limited by the presence of raffinose oligosaccharides (RFO), which are not digested by humans and cause gastrointestinal discomfort. This study explores the potential of α-galactosidases from <em>Penicillium griseoroseum</em> for RFO hydrolysis in soymilk. Two distinct α-galactosidase enzymes, designated α-Gal1 and α-Gal2, were purified using a combination of ion-exchange chromatography and native polyacrylamide gel electrophoresis. Both enzymes exhibited characteristics of multimeric proteins and displayed similar biochemical properties. Optimal activity was observed at a pH range of 4.5–5.0 and a temperature range of 40–45 °C. Notably, α-Gal1 demonstrated high thermostability with a half-life of 16 h at 40 °C. The α-galactosidases displayed different substrate affinitiesfor the substrates ρ-NP-αGal, o-NP-αGal, rD-raffinose, <span>d</span>-stachyose, and mD-melibiose. The Michaelis-Menten constant (Km) values for α-Gal1 were 1.06, 1.31, 28.74, 19.88, and 4.77 mmol/L, respectively, while those for α-Gal2 were 0.8, 1.26, 30.46, 21.74 and 5.01 mmol/L, respectively. Both α-Gal1 and α-Gal2 were strongly inhibited by metal ions (Ag⁺, Cu<sup>2</sup>⁺, Fe<sup>2</sup>⁺, and Hg<sup>2</sup>⁺) and moderately inhibited by <span>d</span>-melibiose. Importantly, both enzymes efficiently hydrolyzed RFOs, achieving complete <span>d</span>-stachyose elimination from soymilk after a 6-h incubation. These findings propose the promising application of these α-galactosidases in industrial soymilk production, potentially enhancing its nutritional value and alleviating gastrointestinal issues in consumers.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Li Zhao , Huizheng Wang , Zanxia Cao , Qiang Li , Zhenghua Li , Liling Zhao , Ying Liu , Zhenling Huang , Enguang Lv
{"title":"Two medicinal molecules Hydralazine and Isoniazid have the potential to control wheat crown rot by combing with a N-acetyltransferase FDB2","authors":"Li Zhao , Huizheng Wang , Zanxia Cao , Qiang Li , Zhenghua Li , Liling Zhao , Ying Liu , Zhenling Huang , Enguang Lv","doi":"10.1016/j.bbrc.2024.150893","DOIUrl":"10.1016/j.bbrc.2024.150893","url":null,"abstract":"<div><div><em>Fusarium pseudograminearum</em> is the main pathogen that causes wheat crown rot (WCR), causing serious harm to wheat production. Wheat secretes Benzoxazolinones (Bxs) as fungicidins to prevent <em>F. pseudograminearum</em> infection. Fusarium Detoxification of Bx 2 (FDB2) can degrade Bx to non-fungitoxic N-(2-hydroxyphenyl) malonamic acid. Therefore, FDB2 may be a potential drug target for WCR.</div><div>In the present study, the structure of FDB2 was determined using the molecular replacement method. The overall FDB2 structure displayed a typical N-acetyltransferase (NAT1) conformation. Unlike other NAT1s, the active site cleft is divided into two parts by a long loop (A<sup>135</sup>MSPYPDVRKNQA<sup>147</sup>). Hydralazine, Isoniazid, and 2,4′-dibromoacetanilide were screened out as potential inhibitors of FDB2 by structure alignment. Affinity measurements by MST showed that FDB2 prefers to combine Isoniazid and Hydralazine rather than its natural substrate, 2-aminophenol. Wheat seedling infection assays showed that Isoniazid and Hydralazine suppress <em>F. pseudograminearum</em> invasion in wheat. Our study found that Hydralazine and Isoniazid have the potential to control WCR. This article provides a new idea for the application of medicine, which has serious adverse effects, on plant disease control to reduce research costs and make obsolete drugs shine with vitality.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}