Journal of Biological Chemistry最新文献_第7页

Ancestral evolution of oxidase activity in a class of (S)-nicotine and (S)-6-hydroxynicotine degrading flavoenzymes. 一类(S)-尼古丁和(S)-6-羟尼古丁降解黄酶氧化酶活性的祖先进化。

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2025-06-11 DOI: 10.1016/j.jbc.2025.110360

Zhiyao Zhang, Parth R Bandivadekar, Andrew J Gaunt, Surl-Hee Ahn, Todd J Barkman, Frederick Stull

{"title":"Ancestral evolution of oxidase activity in a class of (S)-nicotine and (S)-6-hydroxynicotine degrading flavoenzymes.","authors":"Zhiyao Zhang, Parth R Bandivadekar, Andrew J Gaunt, Surl-Hee Ahn, Todd J Barkman, Frederick Stull","doi":"10.1016/j.jbc.2025.110360","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110360","url":null,"abstract":"Reduced flavin cofactors have the innate ability to reduce molecular oxygen to hydrogen peroxide. Flavoprotein oxidases turbocharge the reaction of their flavin cofactor with oxygen whereas flavoprotein dehydrogenases generally suppress it, yet our understanding of how these two enzyme classes control this reactivity remains incomplete. Here we used ancestral sequence reconstruction and biochemical characterization to retrace the evolution of oxidase activity in a lineage of nicotine/6-hydroxynicotine degrading enzymes of the flavoprotein amine oxidase superfamily. Our data suggest that the most ancient ancestor that gave rise to this lineage was a dehydrogenase, and that oxidase activity emerged later from within this group of dehydrogenases. We have identified the key amino acid replacements responsible for this emergence of oxidase activity, which, remarkably, span the entire protein structure. Molecular dynamics simulations indicate that this constellation of substitutions decreases the global dynamics of the protein in the evolution of oxidase function. This coincides with a dramatic restriction in the movement of a lysine residue in the active site, which more optimally positions it in front of the flavin to promote the reaction with O2. Our results demonstrate that sites distant from the flavin microenvironment can help control flavin-oxygen reactivity in flavoenzymes by modulating the conformational space and dynamics of the protein and catalytic residues in the active site.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"110360"},"PeriodicalIF":4.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biochemical and structural characterization of a GNAT superfamily protein acetyltransferase from Helicobacter pylori. 幽门螺杆菌GNAT超家族蛋白乙酰转移酶的生化和结构表征。

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2025-06-10 DOI: 10.1016/j.jbc.2025.110356

Venkatareddy Dadireddy, Amrendra Kumar, Sumith Kumar, Siddhartha P Sarma, Pranjal Mahanta, Suryanarayanarao Ramakumar, Rao N Desirazu

{"title":"Biochemical and structural characterization of a GNAT superfamily protein acetyltransferase from Helicobacter pylori.","authors":"Venkatareddy Dadireddy, Amrendra Kumar, Sumith Kumar, Siddhartha P Sarma, Pranjal Mahanta, Suryanarayanarao Ramakumar, Rao N Desirazu","doi":"10.1016/j.jbc.2025.110356","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110356","url":null,"abstract":"Helicobacter pylori (H. pylori), a gastric pathogen with high genetic variability and a unique niche, causes peptic ulcers and gastric cancer. Natural transformation contributes to the genetic variability of H. pylori. To date, protein acetylation and the associated acetyltransferase(s) have not been reported in this bacterium. Here, we report protein acetylation in H. pylori and identify a putative protein acetyltransferase, HP0935, capable of acetylating amino acids and proteins including DNA processing protein A (DprA), which is involved in natural transformation. HP0935 acetylates residue K127 in DprA, important for DNA binding, thus likely to regulate natural transformation. We determined the crystal structures of HP0935 in its apo form and in complex with acetyl-coenzyme A (ACO) to 2.00 Å and 2.40 Å resolution, respectively. Structural analysis revealed a conformational change in substrate-binding loops, α1- α2 and β6-β7, upon ACO binding. Structural comparison showed that HP0935 differs from other protein acetyltransferases in the length and orientation of these loops. Molecular dynamics simulation data suggest that these loops are highly dynamic, and ACO binding could affect their dynamics. Given that several proteins may undergo acetylation in H. pylori and the fact that HP0935 is the only known protein acetyltransferase, the loop dynamics are likely to facilitate the acceptance of multiple substrates by HP0935. Structure-based mutational analysis showed that no general base is required for the enzymatic activity. However, a conserved catalytic water molecule at the active site is likely to serve the purpose. Furthermore, the general acid Y127 is essential for enzymatic activity.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"110356"},"PeriodicalIF":4.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144284495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural basis for the substrate specificity of Helix pomatia AMP deaminase and a chimeric ADGF adenosine deaminase. 螺旋鱼AMP脱氨酶和嵌合ADGF腺苷脱氨酶底物特异性的结构基础。

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2025-06-10 DOI: 10.1016/j.jbc.2025.110357

Gundeep Kaur, John R Horton, George Tzertzinis, Jujun Zhou, Ira Schildkraut, Xiaodong Cheng

{"title":"Structural basis for the substrate specificity of Helix pomatia AMP deaminase and a chimeric ADGF adenosine deaminase.","authors":"Gundeep Kaur, John R Horton, George Tzertzinis, Jujun Zhou, Ira Schildkraut, Xiaodong Cheng","doi":"10.1016/j.jbc.2025.110357","DOIUrl":"10.1016/j.jbc.2025.110357","url":null,"abstract":"Helix pomatia AMP deaminase (HPAMPD), an enzyme enriched in the foot muscle of the mollusk Helix pomatia, exhibits deaminase activity on adenosine-5'-monophosphate (AMP). HPAMPD is the first member of the adenosine deaminase-related growth factor (ADGF) family to prefer the nucleotideAMP over the nucleoside adenosine. To investigate the substrate selectivity of HPAMPD, we determined its structure in both the apo form and in complex with the adenosine analogs pentostatin and pentostatin-5'-monophosphate. Structurally, HPAMPD adopts a fold similar to human ADA2, an ADGF family member. HPAMPD has acquired the ability to interact with the 5'-monophosphate group of AMP through polar and charged residues located in three key structural elements: (1) the loop immediately following strand β1; (2) the loop between helices αH and αI; and (3) the end of strand β5 and its adjacent loop. We engineered a chimeric deaminase by integrating these elements from HPAMPD into another related mollusk nucleoside adenosine deaminase, Aplysia ADGF. The chimeric enzyme efficiently deaminates AMP, demonstrating a gained substrate specificity, while retaining the adenosine deamination activity of Aplysia ADGF. The phosphate-binding feature of HPAMPD is a hallmark of nucleotide deaminases, conserved among AMP and N6-methyl-AMP (6mAMP) deaminases. We discuss the human adenosine deaminases each with distinct substrate specificities for the nucleoside, the nucleotide (AMP), and its methylated form, 6mAMP.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"110357"},"PeriodicalIF":4.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144284497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

BET bromodomain inhibitors attenuate transcription of a subset of IL-1-induced NF-κB targets that promote inflammation in β-cells. BET溴结构域抑制剂可减弱il -1诱导的NF-κB靶点亚群的转录，从而促进β-细胞的炎症。

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2025-06-10 DOI: 10.1016/j.jbc.2025.110358

Joshua A Nord, Savannah J Makowski, Paul F W Sidlowski, Karina L Bursch, John A Corbett, Brian C Smith

{"title":"BET bromodomain inhibitors attenuate transcription of a subset of IL-1-induced NF-κB targets that promote inflammation in β-cells.","authors":"Joshua A Nord, Savannah J Makowski, Paul F W Sidlowski, Karina L Bursch, John A Corbett, Brian C Smith","doi":"10.1016/j.jbc.2025.110358","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110358","url":null,"abstract":"Cytokine-stimulated transcription of NF-κB target genes is linked to the development of multiple inflammatory and autoimmune diseases. Inhibitors of bromodomain and extraterminal domain (BET) epigenetic reader proteins attenuate inflammatory gene transcription and delay the onset of several inflammatory diseases, including autoimmune diabetes. Our previous studies showed that BET bromodomain inhibitors disrupt the interaction between BET family member BRD4 and NF-κB transcription factor p65 in β-cells, thus attenuating cytokine-stimulated NF-κB-dependent gene and functional changes. However, the role of NF-κB in developing inflammatory disease is controversial, as NF-κB inhibition can promote disease progression in some contexts. NF-κB target genes play both physiological and pathophysiological roles in regulating the cellular response to cytokines. Here, using cytokine-stimulated pancreatic β-cells as an inflammatory disease model, we show that NF-κB-dependent gene products that participate in inflammation are sensitive to BET bromodomain inhibition. In contrast, gene products that maintain cellular homeostasis or protect β-cells from stressors are largely insensitive to BET bromodomain inhibition. These studies define a novel and selective role for BET bromodomain-containing proteins in regulating inflammatory gene activation.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"110358"},"PeriodicalIF":4.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144284484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Select Early Growth Response (Egr) isoforms augment Hypoxia Inducible Factor 2 (HIF-2) regulation of erythropoietin (Epo) gene expression in mammals. 选择早期生长反应（Egr）亚型增强哺乳动物缺氧诱导因子2 （HIF-2）调控红细胞生成素（Epo）基因表达。

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2025-06-10 DOI: 10.1016/j.jbc.2025.110355

Jason S Nagati, Elhadji M Dioum, Catarina S Giardinetto, S M Golam Mohiuddin, Qiuyang Zhang, Joseph A Garcia

{"title":"Select Early Growth Response (Egr) isoforms augment Hypoxia Inducible Factor 2 (HIF-2) regulation of erythropoietin (Epo) gene expression in mammals.","authors":"Jason S Nagati, Elhadji M Dioum, Catarina S Giardinetto, S M Golam Mohiuddin, Qiuyang Zhang, Joseph A Garcia","doi":"10.1016/j.jbc.2025.110355","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110355","url":null,"abstract":"Hypoxia Inducible Factors (HIFs) are heterodimeric, oxygen-sensitive, stress-responsive transcription factors in vertebrates composed of one of three alpha components conferring oxygen sensitivity and one of four beta components required for dimerization and DNA binding. The founding alpha member, HIF-1α, is ubiquitously expressed and regulates numerous target genes required for cellular function under physiological hypoxic states. In comparison, HIF-2α is more restricted in its expression, but nevertheless is also required for normal physiological function. The prototypical HIF-2 target gene is erythropoietin (Epo), one of the most highly hypoxia-inducible genes in mammals and in Hep3B cells, a model cell line used to study hypoxia-inducible gene regulation. However, despite cell culture and in vivo data supporting Epo as a preferential HIF-2 target, the molecular basis for selective activation of Epo by HIF-2 remains unknown. In this study, we report identification of novel evolutionary conserved cis-acting elements in the mammalian 3' Epo enhancer region that includes recognition sites for stress-responsive early growth response (Egr) transcription factors, demonstrate that select Egr2 and Egr3 isoforms augment HIF-2 activation of a reported containing the extended 3' Epo enhancer with Egr binding sites, reveal stable Egr2/HIF-2 complex formation in hypoxic Hep3B cells, and provide conditional knockout data from mice supporting an in vivo role for Egr2 in Epo gene regulation. These results provide insights into HIF-2 selective signaling mechanisms with ramifications that extend well beyond Epo regulation.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"110355"},"PeriodicalIF":4.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144284496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bacterial genome encoded ParMs. 细菌基因组编码ParMs。

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2025-06-09 DOI: 10.1016/j.jbc.2025.110351

Samson Ali, Adrian Koh, David Popp, Kotaro Tanaka, Yoshihito Kitaoku, Naoyuki Miyazaki, Kenji Iwasaki, Kaoru Mitsuoka, Robert C Robinson, Akihiro Narita

{"title":"Bacterial genome encoded ParMs.","authors":"Samson Ali, Adrian Koh, David Popp, Kotaro Tanaka, Yoshihito Kitaoku, Naoyuki Miyazaki, Kenji Iwasaki, Kaoru Mitsuoka, Robert C Robinson, Akihiro Narita","doi":"10.1016/j.jbc.2025.110351","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110351","url":null,"abstract":"ParMs generally exist on low copy number plasmids where they contribute to plasmid segregation and stable inheritance. We carried out bioinformatics analysis, which indicated that ParM genes are not only confined to plasmids but are also occasionally found on genomes. Here we report the discovery and characterization of two chromosome encoded ParMs (cParMs) from the genomes of Desulfitobacterium hafniense (Dh-cParM1) and Clostridium botulinum (Cb-cParM). Both cParMs form filaments, exhibit nucleotide hydrolysis, and possess characteristic ParM subunit structures. Dh-cParM1 forms single and tightly coupled double filaments and is highly conserved on the chromosomes of five of six Desulfitobacterium species. Interestingly, these bacteria have not been reported to harbour plasmids. Cb-cParM possesses unique properties. Its filaments were stable after nucleotide hydrolysis and Pi release, and its ParR, (Cb-cParR) did not affect the initial phase of Cb-cParM polymerization but displayed properties of a depolymerization factor for mature filaments. These results indicate functional, polymerizing ParMs can be encoded on genomes, suggesting that ParM roles may extend to other functions beyond plasmid segregation.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"110351"},"PeriodicalIF":4.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High-Throughput Epigenetic Profiling Immunoassays for Accelerated Disease Research and Clinical Development. 加速疾病研究和临床发展的高通量表观遗传分析免疫分析。

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2025-06-07 DOI: 10.1016/j.jbc.2025.110352

Priscilla Van den Ackerveken, Clotilde Hannart, Dorian Pamart, Robin Varsebroucq, Marion Wargnies, Olivia Thiry, Marie Lurkin, Séverine Vincent, Muriel Chapelier, Guillaume Rommelaere, Marielle Herzog

{"title":"High-Throughput Epigenetic Profiling Immunoassays for Accelerated Disease Research and Clinical Development.","authors":"Priscilla Van den Ackerveken, Clotilde Hannart, Dorian Pamart, Robin Varsebroucq, Marion Wargnies, Olivia Thiry, Marie Lurkin, Séverine Vincent, Muriel Chapelier, Guillaume Rommelaere, Marielle Herzog","doi":"10.1016/j.jbc.2025.110352","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110352","url":null,"abstract":"Epigenetics, which examines the regulation of genes without modification of the DNA sequence, plays a crucial role in various biological processes and disease mechanisms. Among the different forms of epigenetic modifications, histone post-translational modifications (PTMs) are important for modulating chromatin structure and gene expression. Aberrant levels of histone PTMs are implicated in a wide range of diseases, including cancer, making them promising targets for biomarker discovery and therapeutic intervention. In this context, blood, tissues, or cells serve as valuable resources for epigenetic research and analysis. Traditional methods such as mass spectrometry and western blotting are widely used to study histone PTMs, providing qualitative and (semi)quantitative information. However, these techniques often face limitations that could include throughput and scalability, particularly when applied to clinical samples. To overcome these challenges, we developed and validated 13 Nu.Q® immunoassays to detect and quantify specific histone PTM-nucleosomes from K2EDTA plasma samples. Then, we tested these assays on other types of samples, including chromatin extracts from frozen tissues, as well as cell lines and white blood cells Our findings demonstrate that the Nu.Q® assays offer high specificity, sensitivity, precision and linearity, making them effective tools for epigenetic profiling. A comparative analysis of HeLa cells using mass spectrometry, Western blot, and Nu.Q® immunoassays revealed a consistent histone PTMs signature, further validating the effectiveness of these assays. Additionally, we successfully applied Nu.Q® assays across various biological samples, including human tissues from different organs and specific white blood cell subtypes, highlighting their versatility and applicability in diverse biological contexts.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"110352"},"PeriodicalIF":4.0,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The sphingosine-1-phosphate receptor 2 S1PR2 mediates chronic glucocorticoid exposure-induced hepatic steatosis and hypertriglyceridemia. 鞘氨醇-1-磷酸受体2 S1PR2介导慢性糖皮质激素暴露诱导的肝脂肪变性和高甘油三酯血症。

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2025-06-07 DOI: 10.1016/j.jbc.2025.110353

Maggie Chang, Michelle Zhao, Emily M Whang, Rebecca A Lee, Donald K Scott, Jen-Chywan Wang

{"title":"The sphingosine-1-phosphate receptor 2 S1PR2 mediates chronic glucocorticoid exposure-induced hepatic steatosis and hypertriglyceridemia.","authors":"Maggie Chang, Michelle Zhao, Emily M Whang, Rebecca A Lee, Donald K Scott, Jen-Chywan Wang","doi":"10.1016/j.jbc.2025.110353","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110353","url":null,"abstract":"Glucocorticoids are potent anti-inflammatory agents that are frequently used to treat inflammatory and autoimmune diseases. Chronic glucocorticoid treatment, however, causes unwanted adverse effects such as hypertriglyceridemia and hepatic steatosis. Here we showed that reducing the expression of sphingosine-1-phosphate receptor 2 (S1PR2) in mice liver reduced chronic glucocorticoid exposure induced triglyceride accumulation in the liver and the plasma. Chronic glucocorticoid treatment increased the recruitment of sterol regulatory element-binding protein 1c (Srebp1c) to the sterol regulatory element of mouse fatty acid synthase (Fasn) gene. This response was attenuated in hepatic S1PR2 knockdown mice. Chronic glucocorticoid treatment also increased the recruitment of carbohydrate response element binding protein (ChREBP) to the carbohydrate response elements (ChoREs) of lipogenic and glycolytic genes. This response was partially reduced in hepatic S1PR2 knockdown mice. Reducing hepatic ChREBP expression reduced the expression of Pklr, Me1, and Fasn. However, long-term glucocorticoid induced triglyceride accumulation in the liver and the plasma were not affected whereas the hepatic lactate levels were decreased. Thus, ChREBP plays a major role in chronic glucocorticoid induced glycolysis whereas its role in hypertriglyceridemia and hepatic steatosis was modest. Overall, this study demonstrated that hepatic S1PR2 signaling plays a partial but significant role in chronic glucocorticoid exposure-activated Srebp1c and ChREBP which promote lipogenesis and glycolysis, respectively.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"110353"},"PeriodicalIF":4.0,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Analysis of chondroitin degradation by components of a Bacteroides caccae polysaccharide utilization locus. 一种拟杆菌多糖利用位点组分降解软骨素的分析。

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2025-06-07 DOI: 10.1016/j.jbc.2025.110354

Bernadette Alvarez, Olivia F Canil, Kristin E Low, Andrew G Hettle, D Wade Abbott, Alisdair B Boraston

{"title":"Analysis of chondroitin degradation by components of a Bacteroides caccae polysaccharide utilization locus.","authors":"Bernadette Alvarez, Olivia F Canil, Kristin E Low, Andrew G Hettle, D Wade Abbott, Alisdair B Boraston","doi":"10.1016/j.jbc.2025.110354","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110354","url":null,"abstract":"The human gut microbiota (HGM) possesses enormously diverse capacity to metabolize both host and dietary glycans. Glycosaminoglycans (GAG) are complex polysaccharides that may be in the diet (e.g., from animal products) or may be presented by host tissues. These polysaccharides are known to be prioritized as a nutrient source by some members of the HGM. While significant advances in understanding how GAGs are metabolized by the HGM have been made, the varied architectures of the numerous polysaccharide utilization loci (PULs) targeting varied polysaccharides suggest that all the mechanisms of GAG degradation may not have been uncovered. Here we show that components of a (PUL) from Bacteroides caccae have activities consistent with comprising a unique pathway for depolymerization of chondroitin sulfate, a common GAG. After prior desulfation by an endo-sulfatase, BcSulf, to produce unsulfated chondroitin from chondroitin, the depolymerization pathway begins with the activity a polysaccharide lyase from family 35, BcPL35. BcPL35 activity is coupled with BcGH88, an exo-β-uronyl hydrolase, and presumably BcGH109, a confirmed α/β-N-acetylgalactosaminidase. The most unique feature of the pathway is a β-D-glucuronate dehydratase, BcGDH, which we show through structural and functional analyses primes saturated non-reducing end β-D-glucuronate residues for hydrolysis by BcGH88. BcGDH is a member of a large family previously classified as glycoside hydrolase family 154. The potential reclassification of GH154 enzymes as uronate sugar dehydratases not only improves our understanding of chondroitin metabolism by B. caccae but will be broadly applicable to predicting the function of other pathways relevant to uronate sugar metabolism.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"110354"},"PeriodicalIF":4.0,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Staphylococcus aureus as an emerging model to study bacterial cell division. 金黄色葡萄球菌作为研究细菌细胞分裂的新兴模型。

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2025-06-06 DOI: 10.1016/j.jbc.2025.110343

Félix Ramos-León, Kumaran S Ramamurthi

{"title":"Staphylococcus aureus as an emerging model to study bacterial cell division.","authors":"Félix Ramos-León, Kumaran S Ramamurthi","doi":"10.1016/j.jbc.2025.110343","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110343","url":null,"abstract":"Research on bacterial cell division has traditionally focused on rod-shaped model organisms such as Escherichia coli and Bacillus subtilis. While these models have been important in uncovering broadly conserved factors involved in bacterial cell division, the assortment of bacterial shapes, cell wall structures, and lifestyles highlights the need to broaden the scope of study. This includes not only understanding how conserved mechanisms are adapted to diverse cellular morphologies but also discovering mechanisms that arise as specific adaptations to unique cellular shapes. In this context, alternative models such as Staphylococcus aureus are emerging to provide insight into how Gram-positive cocci overcome the challenge of lacking obvious cellular polarity to ensure accurate placement of the division septum and undergo binary fission. In this review, we highlight recent research that reveals how S. aureus performs several distinct but interrelated processes, including peptidoglycan assembly, placement of the cell division septum, and how the division septum can be used as a hub for modifying the peptidoglycan to decorate the cell surface of S. aureus.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"110343"},"PeriodicalIF":4.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0