Biochemistry Biochemistry最新文献_第2页

Structural Characteristics of Docosahexaenoic Acid and Eicosapentaenoic Acid Inhibiting Amyloid-β Fibrillation. 二十二碳六烯酸和二十碳五烯酸抑制淀粉样蛋白-β纤颤的结构特征。

IF 3 3区生物学

Biochemistry Biochemistry Pub Date : 2025-09-24 DOI: 10.1021/acs.biochem.5c00293

Taiyo Yokoi, Ken'ichiro Hayashi, Takashi Morihara, Toshiyuki Murai

引用次数: 0

Dynamic Conformations of Chromatin Remodeler ISWI during Nucleosome Sliding Revealed by Hydrogen-Deuterium Exchange Coupled to Mass Spectrometry. 氢-氘交换耦合质谱法揭示核小体滑动过程中染色质重塑剂ISWI的动态构象。

IF 3 3区生物学

Biochemistry Biochemistry Pub Date : 2025-09-22 DOI: 10.1021/acs.biochem.5c00330

Younus A Bhat, Javaid Y Bhat, Suhail A Shiek, Mohmmad Abaas Dar, Shajrul Amin, Craig L Peterson, Jayant B Udgaonkar, Ajazul H Wani

{"title":"Dynamic Conformations of Chromatin Remodeler ISWI during Nucleosome Sliding Revealed by Hydrogen-Deuterium Exchange Coupled to Mass Spectrometry.","authors":"Younus A Bhat, Javaid Y Bhat, Suhail A Shiek, Mohmmad Abaas Dar, Shajrul Amin, Craig L Peterson, Jayant B Udgaonkar, Ajazul H Wani","doi":"10.1021/acs.biochem.5c00330","DOIUrl":"https://doi.org/10.1021/acs.biochem.5c00330","url":null,"abstract":"Chromatin remodelers maintain the chromatin structure and hence gene expression. Imitation SWItch, ISWI, is a chromatin remodeler, which regulates nucleosome spacing across the genome by its adenosine 5'-triphosphate (ATP)-dependent nucleosome sliding activity. To understand how this happens requires identification of the conformational changes that occur in all domains of ISWI during the entire nucleosome sliding cycle. Using the hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS) methodology, we have monitored the conformational dynamics of Drosophila FL-ISWI at all the stages of nucleosome sliding. Our data show that, in the resting state, FL-ISWI is intrinsically dynamic in many regions, including the N- and C-terminal regulatory regions. During nucleosome sliding, different regions of the ATPase domain, which bind to the nucleosomal DNA, undergo a major conformational change, and the C-terminal HSS domain switches from a stable state to a more dynamic state. ISWI adopts distinct conformations in its nucleosome bound and sliding states as the interactions established by it upon binding to the nucleosome are broken during DNA translocation. HDX-MS has made it possible to characterize multiscale dynamics from small fluctuations to large structural changes occurring in all the domains of FL-ISWI during the different steps of nucleosome sliding. The structural mechanism revealed for ISWI has implications for several other protein families containing a Rec-A domain ATPase core.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123785","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}

引用次数: 0

Biased Agonists of the Type 1 Angiotensin II Receptor Promote Distinct Subcellular β-Arrestin Conformations. 1型血管紧张素II受体的偏向激动剂促进不同的亚细胞β-阻滞构象。

IF 3 3区生物学

Biochemistry Biochemistry Pub Date : 2025-09-20 DOI: 10.1021/acs.biochem.4c00884

Anand Chundi, Uyen Pham, Srikrishna Darbha, Sudarshan Rajagopal

{"title":"Biased Agonists of the Type 1 Angiotensin II Receptor Promote Distinct Subcellular β-Arrestin Conformations.","authors":"Anand Chundi, Uyen Pham, Srikrishna Darbha, Sudarshan Rajagopal","doi":"10.1021/acs.biochem.4c00884","DOIUrl":"https://doi.org/10.1021/acs.biochem.4c00884","url":null,"abstract":"G protein-coupled receptors (GPCRs) are central to cellular signaling and therapeutic targeting. Ligands that activate the same GPCR can selectively activate some signaling pathways over others, a phenomenon termed biased agonism. Additionally, the same ligand and receptor complex can elicit distinct signaling profiles in different subcellular locations (location bias). Here, we examine how various biased agonists influence the recruitment of β-arrestins 1 and 2 induced by the angiotensin II type 1 receptor at the receptor, plasma membrane, and early endosomes. We also assessed β-arrestin conformational states at the receptor and plasma membrane. Using split luciferase and BRET assays, we demonstrate that angiotensin II, its G protein-biased analogs (TRV055, TRV056), and its β-arrestin-biased analogs (TRV023, TRV026, TRV027, TRV034) functionally stratify into two clusters. G protein-biased agonists and AngII predominantly favor a receptor-β-arrestin core complex conformation driven by engagement of the β-arrestin finger loop with the receptor core. In contrast, β-arrestin-biased agonists promote a tail complex configuration of receptor-associated β-arrestins. However, the conformations of β-arrestins monitored at the plasma membrane were found to be unaffected by ligand bias. Furthermore, balanced and G protein-biased ligands induced higher levels of ERK activation in subcellular locations (nucleus, cytosol, and early endosomes) over the β-arrestin-biased ligands, but equal ERK activity at the plasma membrane. Our findings highlight the interplay between ligand and location biases in dictating GPCR signaling, revealing new insights into the molecular mechanisms driving selective signal propagation.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145090720","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}

引用次数: 0

Optimized 3'-Phosphoadenosine-5'-phosphosulfate Biosynthesis via Yeast-Powered ATP Regeneration and Biotin-Streptavidin Enzyme Immobilization. 酵母驱动ATP再生和生物素-链亲和素酶固定化优化3'-磷酸腺苷-5'-硫酸磷酸生物合成。

IF 3 3区生物学

Biochemistry Biochemistry Pub Date : 2025-09-18 DOI: 10.1021/acs.biochem.5c00373

Xin-Yu Li, Jian-Qun Deng, Yu-Han Zhao, Ya-Lin Cao, Yi Li, Jin Hou, Xue-Ping Guo, Ju-Zheng Sheng

{"title":"Optimized 3'-Phosphoadenosine-5'-phosphosulfate Biosynthesis via Yeast-Powered ATP Regeneration and Biotin-Streptavidin Enzyme Immobilization.","authors":"Xin-Yu Li, Jian-Qun Deng, Yu-Han Zhao, Ya-Lin Cao, Yi Li, Jin Hou, Xue-Ping Guo, Ju-Zheng Sheng","doi":"10.1021/acs.biochem.5c00373","DOIUrl":"https://doi.org/10.1021/acs.biochem.5c00373","url":null,"abstract":"3'-Phosphoadenosine-5'-phosphosulfate (PAPS), a universal sulfate donor for sulfation reactions, is indispensable for synthesizing bioactive molecules including therapeutic glycosaminoglycans and sulfolipids; however, its enzymatic production on an industrial scale is constrained by ATP overconsumption and the limited free enzyme reusability. We report an integrated biocatalytic platform combining ATP regeneration with affinity immobilization to enable sustainable PAPS biosynthesis. A polyphosphate kinase-driven ATP regeneration system achieved 86% PAPS conversion efficiency by regenerating ADP using low-cost polyphosphate. Biotin-streptavidin affinity immobilization enhanced operational stability, retaining >50% activity over six reuse cycles with a cumulative PAPS titer of 12.02 g/L. Coupling adenosine-converting Saccharomyces cerevisiae whole-cell catalysts with this system decreased substrate costs by 80.7% and delivered 96% molar PAPS yield from adenosine. This work provides a sustainable platform for industrial PAPS biosynthesis to promote sulfated biomolecule production, including glycosaminoglycans and other therapeutics.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084557","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}

引用次数: 0

Structure-Activity Relationship of an All-α-helical Prenyltransferase Reveals the Mechanism of Indole Prenylation. 全α-螺旋型戊烯基转移酶的构效关系揭示吲哚戊烯化的机制。

IF 3 3区生物学

Biochemistry Biochemistry Pub Date : 2025-09-18 DOI: 10.1021/acs.biochem.5c00329

Takumi Oshiro, Shuta Uehara, Arisa Suto, Yoshikazu Tanaka, Takuya Ito, Yoshio Kodera, Takashi Matsui

{"title":"Structure-Activity Relationship of an All-α-helical Prenyltransferase Reveals the Mechanism of Indole Prenylation.","authors":"Takumi Oshiro, Shuta Uehara, Arisa Suto, Yoshikazu Tanaka, Takuya Ito, Yoshio Kodera, Takashi Matsui","doi":"10.1021/acs.biochem.5c00329","DOIUrl":"https://doi.org/10.1021/acs.biochem.5c00329","url":null,"abstract":"Enzymes are involved in the biosynthesis of a variety of secondary metabolites found in nature. The catalytic mechanism is regulated by the three-dimensional structure of the enzyme, particularly at the catalytic site, resulting in the synthesis of natural products with complex conformations derived from a regioselective, chemoselective, or stereoselective preference of the enzyme reaction. Prenyltransferase, which belongs to the prenylsynthase superfamily, catalyzes the condensation of isoprene to an aromatic compound, consequently producing a terpenoid scaffold structure. Prenyltransferase thus plays an important role in expanding the chemical diversity of the terpenoids. Although the three-dimensional structures of prenylsynthases categorized in the same superfamily have been resolved, the catalytic mechanism of prenyltransferase has been veiled. In this study, we determined the X-ray crystal structure of a novel prenyltransferase, Ord1, which is derived from Streptomyces. Here, we report the enzymatic characteristics of the Ord1 and discuss its catalytic mechanism.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084488","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}

引用次数: 0

Nucleic Acid Sequence Determinants of Transcriptional Pausing by the Human Mitochondrial RNA Polymerase (POLRMT). 人类线粒体RNA聚合酶（POLRMT）转录暂停的核酸序列决定因素。

IF 3 3区生物学

Biochemistry Biochemistry Pub Date : 2025-09-17 DOI: 10.1021/acs.biochem.5c00236

An H Hsieh, Tatiana V Mishanina

{"title":"Nucleic Acid Sequence Determinants of Transcriptional Pausing by the Human Mitochondrial RNA Polymerase (POLRMT).","authors":"An H Hsieh, Tatiana V Mishanina","doi":"10.1021/acs.biochem.5c00236","DOIUrl":"10.1021/acs.biochem.5c00236","url":null,"abstract":"Transcription by RNA polymerase (RNAP) lies at the heart of gene expression in all organisms. The speed with which RNAPs produce RNA is tuned, in part, by signals in the transcribed nucleic acid sequences, which temporarily arrange RNAPs into a paused conformation that is unable to extend the RNA. In turn, the altered transcription kinetics of paused RNAPs determine the three-dimensional shape into which RNA ultimately folds and promote or inhibit cotranscriptional events. While pause sequence determinants have been characterized for multisubunit RNAPs in bacteria and in eukaryotic nuclei, this information is lacking for the single-subunit, T-odd phage-like RNAP of human mitochondria, POLRMT. Here, we developed a robust nucleic acid scaffold system to reconstitute POLRMT transcription in vitro and identified multiple transcriptional pause sites on the human mitochondrial DNA (mtDNA). Using one of the pause sequences as a representative, we performed a suite of mutational studies to pinpoint the nucleic acid elements that enhance, weaken, or completely abolish POLRMT pausing. Based on these mutational results, we constructed a consensus pause motif expected to cause strong pausing for POLRMT: 5'-R-10NNNNNNNGT-1G+1-3', where -1 is the 3' nascent RNA nucleotide in the POLRMT active site, +1 is the incoming NTP to be added to the nascent RNA, R is A or G, and N is any base. Strikingly, most of the consensus pause elements in this motif are the same for multisubunit prokaryotic and nuclear RNAPs, hinting at potentially shared features of the pausing mechanism despite the structural differences between polymerases. Finally, a search of the human mtDNA for this pause motif revealed multiple predicted pause sites with potential roles in mitochondrial cotranscriptional processes.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074176","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}

引用次数: 0

IGPR-1 Is Phosphorylated on the Immunoreceptor Tyrosine-Based Motif, Stimulates the AKT Pathway and Supports Melanoma Growth. IGPR-1在免疫受体酪氨酸基序上磷酸化，刺激AKT通路并支持黑色素瘤生长。

IF 3 3区生物学

Biochemistry Biochemistry Pub Date : 2025-09-16 DOI: 10.1021/acs.biochem.5c00393

Nader Rahimi, Sreesaisowmya Potluri, Vipul Chitalia

{"title":"IGPR-1 Is Phosphorylated on the Immunoreceptor Tyrosine-Based Motif, Stimulates the AKT Pathway and Supports Melanoma Growth.","authors":"Nader Rahimi, Sreesaisowmya Potluri, Vipul Chitalia","doi":"10.1021/acs.biochem.5c00393","DOIUrl":"https://doi.org/10.1021/acs.biochem.5c00393","url":null,"abstract":"Immunoglobulin (Ig) and Proline-rich Receptor-1 (IGPR-1, also called TMIGD2) is closely related to immune checkpoint CD28/PDL1 family receptors. It controls important cellular processes, including immune cell regulation, cell-cell adhesion, mechanosensing, and autophagy, and its activity is associated with multiple human malignancies. However, the role and signaling mechanism of IGPR-1 remains largely undefined. Here, we report that IGPR-1's pro-tumor signaling in melanoma cells is mediated by phosphorylation of the immunoreceptor tyrosine-based activation motif (ITAM) tyrosine (Y222). IGPR-1 is phosphorylated at Y222 in human melanoma tissues and cell lines. Phosphorylation of Y222 is context-dependent and catalyzed by EGFR and Src kinase. Pharmacological inhibition of EGFR using Erlotinib, as well as EGFR knockdown via shRNA, suppressed phosphorylation of Y222. In contrast, stimulation with EGF enhanced Y222 phosphorylation in vivo, and recombinant active EGFR directly phosphorylated Y222 in an in vitro kinase assay. In vivo coimmunoprecipitation and in vitro GST pull-down assays demonstrated that phospho-Y222 facilitates the binding of IGPR-1 with the SH2 domain-containing protein SHC1. IGPR-1 stimulates multiple key downstream signal transduction pathways relevant to tumorigenesis, including AKT, mTOR, and MAPK pathways. Mutation of Y222 blocked IGPR-1-mediated activation of AKT and MAPK, leading to the inhibition of tumor spheroid growth. This study uncovered new findings that have potential diagnostic and therapeutic implications in melanoma.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074112","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}

引用次数: 0

Correction to "Computational Characterization of the Interaction of CARD Domains in the Apoptosome". 对“凋亡细胞中CARD结构域相互作用的计算表征”的修正。

IF 3 3区生物学

Biochemistry Biochemistry Pub Date : 2025-09-16 DOI: 10.1021/acs.biochem.5c00490

Rita Ortega-Vallbona, Linda Johansson, Laureano E Carpio, Eva Serrano-Candelas, Sayyed Jalil Mahdizadeh, Howard Fearnhead, Rafael Gozalbes, Leif A Eriksson

引用次数: 0

Structure of Bovine Glycine N-Acyltransferase Clarifies Its Catalytic Mechanism. 牛甘氨酸n -酰基转移酶的结构及其催化机理。

IF 3 3区生物学

Biochemistry Biochemistry Pub Date : 2025-09-12 DOI: 10.1021/acs.biochem.5c00315

Ana C Ebrecht, Christoffel P S Badenhorst, Uwe T Bornscheuer, Randy J Read, Diederik J Opperman, Alberdina A van Dijk

引用次数: 0

MksEF Accessory Proteins Inhibit MksB ATPase Activity and Modulate DNA Substrate Binding. MksEF辅助蛋白抑制MksB atp酶活性并调节DNA底物结合。

IF 3 3区生物学

Biochemistry Biochemistry Pub Date : 2025-09-09 DOI: 10.1021/acs.biochem.5c00151

Pratibha Kumari, Shamila Minnu K C, Teasha Biswas, Vinayak Hegde, Umesh Appaiah, M Dharma Prasad, Kunal Sharan, Dhabaleswar Patra, Ravi Kumar

{"title":"MksEF Accessory Proteins Inhibit MksB ATPase Activity and Modulate DNA Substrate Binding.","authors":"Pratibha Kumari, Shamila Minnu K C, Teasha Biswas, Vinayak Hegde, Umesh Appaiah, M Dharma Prasad, Kunal Sharan, Dhabaleswar Patra, Ravi Kumar","doi":"10.1021/acs.biochem.5c00151","DOIUrl":"https://doi.org/10.1021/acs.biochem.5c00151","url":null,"abstract":"Chromosome organization and segregation are fundamental processes across all domains of life. In bacteria, the mechanisms governing nucleoid organization remain poorly understood. This study investigates the function of an alternative structural maintenance of chromosomes (SMC) complex, MksBEF, in Mycobacterium smegmatis. We show that MksB, the SMC subunit of the complex, binds DNA and plays a crucial role in local chromosome organization, a function distinct from that of other condensins. We successfully reconstituted the MksBEF complex and determined its stoichiometry as MksB2E4F2 using gel filtration and ultracentrifugation. Gel shift assays and isothermal titration calorimetry reveal that the accessory proteins MksE and MksF interact with MksB and significantly enhance its DNA-binding affinity─an effect not observed in SMC or MukB-associated accessory proteins. Furthermore, ANS-based fluorescence experiments indicate that DNA binding induces structural rearrangements in both MksB alone and the MksBEF complex. Notably, although MksEF enhances the DNA-binding affinity of MksB, it also markedly suppresses its ATPase activity, a unique regulatory mechanism distinct from other SMC complexes. These findings provide mechanistic insights into how MksE and MksF modulate MksB activity, advancing our understanding of chromosome dynamics in mycobacteria.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022459","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}

引用次数: 0