Biochemistry Biochemistry最新文献_第6页

Correction to “Key Disulfide Bonds in an Insect Hormone Binding Protein: cDNA Cloning of a Juvenile Hormone Binding Protein of Heliothis Virescens and Ligand Binding by Native and Mutant Forms” 修正“昆虫激素结合蛋白的关键二硫键：Heliothis Virescens幼代激素结合蛋白的cDNA克隆及天然和突变形式的配体结合”

IF 2.7 3区生物学

Biochemistry Biochemistry Pub Date : 2026-09-01 Epub Date: 2026-08-17 DOI: 10.1021/acs.biochem.6c00552

Hubert Wojtasek, Glenn D. Prestwich

引用次数: 0

Structural and Functional Insights into pH-Dependent Dynamics of Ostrinia furnacalis Pheromone-Binding Protein 3 (OfurPBP3) 玉米螟信息素结合蛋白3 (OfurPBP3) ph依赖性动态的结构和功能研究。

IF 2.7 3区生物学

Biochemistry Biochemistry Pub Date : 2026-09-01 Epub Date: 2026-06-10 DOI: 10.1021/acs.biochem.6c00272

Pratikshya Paudel, Omar Al Danoon, Ahmad Tijani Azeez, Smita Mohanty

{"title":"Structural and Functional Insights into pH-Dependent Dynamics of Ostrinia furnacalis Pheromone-Binding Protein 3 (OfurPBP3)","authors":"Pratikshya Paudel, Omar Al Danoon, Ahmad Tijani Azeez, Smita Mohanty","doi":"10.1021/acs.biochem.6c00272","DOIUrl":"10.1021/acs.biochem.6c00272","url":null,"abstract":"Male moths of Ostrinia furnacalis (Asian corn borer) rely on a highly sensitive olfactory system todetect female-emitted sex pheromones essential for mating. Pheromone-bindingproteins (PBPs), expressed in male antennae, transport hydrophobicpheromones through the aqueous sensillar lymph to olfactory receptors.OfurPBP3, a male-biased PBP, plays a key role in species-specificpheromone detection. Here, we report the cloning, recombinant expression,refolding, purification, and structural characterization of OfurPBP3.Fluorescence binding assays revealed high nanomolar affinity for both E- and Z-isomers of tetradec-12-en-1-ylacetate pheromone. Circular dichroism and NMR studies demonstratedthat although OfurPBP3 retains a predominantly α-helical secondarystructure under acidic conditions, its tertiary structure is perturbed,exhibiting increased conformational dynamics and features consistentwith partial unfolding. Upon restoration to pH 6.5, the native tertiarystructure is recovered, indicating that the pH-induced structuralchanges are reversible. Homology modeling predicted a conserved PBPfold containing a hydrophobic pocket. Molecular docking studies identifiedresidues potentially involved in ligand recognition. The behaviorsof OfurPBP3 in acidic pH are reminiscent of the molten-globule–likestates previously reported for other pheromone-binding proteins from Ostrinia species. Collectively, these findings suggest thatligand release in Ostrinia PBPs is associated withpH-dependent structural destabilization and partial unfolding, ratherthan a canonical two-state (open ⇌ closed) conformational switchas described for several other lepidopteran PBPs, such as ApolPBP1.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":"65 17","pages":"2661–2671"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148215365","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}

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Recognition of Single-Strand-Duplex Junctions in RNA Using Peptide Nucleic Acids That Form Watson–Crick and Hoogsteen Hydrogen Bond 利用形成沃森-克里克和胡格斯汀氢键的肽核酸识别RNA中的单链-双链连接

IF 2.7 3区生物学

Biochemistry Biochemistry Pub Date : 2026-09-01 Epub Date: 2026-08-18 DOI: 10.1021/acs.biochem.6c00386

Sara Farshineh Saei, Eriks Rozners

{"title":"Recognition of Single-Strand-Duplex Junctions in RNA Using Peptide Nucleic Acids That Form Watson–Crick and Hoogsteen Hydrogen Bond","authors":"Sara Farshineh Saei, Eriks Rozners","doi":"10.1021/acs.biochem.6c00386","DOIUrl":"https://doi.org/10.1021/acs.biochem.6c00386","url":null,"abstract":"Sequence-specificrecognition of complex, folded RNA structuresis a highly desirable yet formidable goal. The present study explorednucleobase-modified peptide nucleic acids (PNAs) as ligands that bindand recognize junctions between single- and double-stranded RNA viaWatson–Crick and Hoogsteen hydrogen bonding, respectively.The results showed that these hybrid PNAs exhibited strong affinityfor RNA junctions and transitioned from duplex to triplex bindingmodes without additional modification. However, depending on the sequencecontext, extending the PNA’s backbone at the transition sitecould yield a slight improvement in binding affinity. The overallbinding affinity was modest and comparable to that of triplex-onlybinding. The duplex–triplex binding mode exhibited relativelylow sensitivity to mismatches adjacent to the transition site, suggestingthat the transition might be dynamic and not well organized. Overall,the results demonstrated PNA’s ability to recognize single–double-strandjunctions in RNA; however, the modest stability and specificity mightlimit this binding mode to specific cases where simpler duplex ortriplex binding modes are not feasible.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":"65 17","pages":"2672–2678"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148861366","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

A Molecular Mechanistic Deep Dive into 14–3–3 Molecular Glue Cooperativity 14-3-3分子胶协同性的分子机制深入研究

IF 2.7 3区生物学

Biochemistry Biochemistry Pub Date : 2026-09-01 Epub Date: 2026-08-17 DOI: 10.1021/acs.biochem.6c00427

Marloes A. M. Pennings, Edmee M. F. Vandenboorn-Bönner, Lisa Nooren, Markella Konstantinidou, Chad Altobelli, Christian Ottmann, Albert J. Markvoort, Galen P. Miley, Michelle R. Arkin, Luc Brunsveld

{"title":"A Molecular Mechanistic Deep Dive into 14–3–3 Molecular Glue Cooperativity","authors":"Marloes A. M. Pennings, Edmee M. F. Vandenboorn-Bönner, Lisa Nooren, Markella Konstantinidou, Chad Altobelli, Christian Ottmann, Albert J. Markvoort, Galen P. Miley, Michelle R. Arkin, Luc Brunsveld","doi":"10.1021/acs.biochem.6c00427","DOIUrl":"https://doi.org/10.1021/acs.biochem.6c00427","url":null,"abstract":"Molecular glues (MGs)stabilize protein–protein interactions(PPIs) through interactions at composite binding interfaces, therebypromoting cooperative ternary complex formation. For hub proteinsthat engage in multiple PPIs with widely varying intrinsic affinities,the interplay between binary PPI affinity and MG cooperativity istherefore a key determinant of selective stabilization. Here, we usethe multiclient 14–3–3 scaffold protein as a model systemto systematically dissect the relationship between binary 14–3–3/clientaffinity (KDI) and MG-induced cooperativity(α). Client peptide affinity was systematically tuned by modifyingresidues N-terminal to the phosphorylated 14–3–3 bindingmotif while preserving the C-terminal composite interface requiredfor MG recognition. Using a combination of biophysical techniquesand protein crystallography, we show that changes in KDI alter the thermodynamic and kinetic parameters of bothbinary and ternary complex formation, but do not affect MG cooperativity.This principle was observed for the noncovalent MG fusicoccin-A aswell as covalent MGs targeting 14–3–3σ/clientcomplexes. Competitive binding experiments and thermodynamic modelingfurther revealed that, although α is independent of KDI, the interplay between KDI, MGaffinity (KDII), and cooperativity determineswhich PPIs are preferentially stabilized in a multiclient environment.Together, these findings establish cooperativity, intrinsic PPI affinity,and MG affinity as key parameters governing MG activity and selectivity,providing a framework for the rational design of MGs targeting hubprotein interactomes.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":"65 17","pages":"2769–2783"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148861417","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}

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The Photocycle of the Red Light-Sensitive Plant-like Cryptochrome CryP from Phaeodactylum tricornutum 三角褐指藻（Phaeodactylum tricornutum）红色光敏类植物隐色素CryP的光循环

IF 2.7 3区生物学

Biochemistry Biochemistry Pub Date : 2026-09-01 Epub Date: 2026-08-23 DOI: 10.1021/acs.biochem.6c00479

Marius F. Nagel, Maximilian Steiner, Niklas C. J. Wenner, Claudia Büchel, Tilman Kottke

{"title":"The Photocycle of the Red Light-Sensitive Plant-like Cryptochrome CryP from Phaeodactylum tricornutum","authors":"Marius F. Nagel, Maximilian Steiner, Niklas C. J. Wenner, Claudia Büchel, Tilman Kottke","doi":"10.1021/acs.biochem.6c00479","DOIUrl":"https://doi.org/10.1021/acs.biochem.6c00479","url":null,"abstract":"Cryptochromes actas photoreceptors in diverse organismsand bindflavin adenine dinucleotide (FAD) as a chromophore. The plant-likecryptochrome CryP from the diatom Phaeodactylum tricornutum regulates in vivo the expression of light-harvestingproteins in response to blue light. CryP carries, in addition, 5,10-methenyltetrahydrofolate(MTHF) for light capturing. In contrast to most other cryptochromes,FAD in CryP is present as a stable flavin neutral radical in the dark,which undergoes a photoreduction to form the fully reduced state inthe light. Here, we demonstrate by applying nanosecond-time-resolvedUV–vis spectroscopy that the flavin neutral radical is photoreducedwithin 100 ns to the fully reduced state and subsequently recoversvery fast with a time constant of 1.4 ms in the absence of reducingagents or in the presence of 1 mM dithiothreitol. Despite its shortlifetime, the transient light state is sufficient to induce homo-oligomerizationof CryP as shown by light-dependent size exclusion chromatography.A long-lived fully reduced flavin is only formed in the presence ofexternal reducing agents by a second pathway that is lost after asingle full conversion, likely by degradation. Then, the recoveryto the neutral radical state takes hours with a time constant of 40min. Moreover, we validate the existence of energy transfer betweenthe two chromophores depending on the flavin redox state using fluorescencespectroscopy. We propose a detailed mechanism for the photocycle ofCryP, highlighting the contribution of two separate reduction pathways.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":"65 17","pages":"2756–2768"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148870362","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

Designed NIR-I Emissive and Selective G-Quadruplex DNA Binder with Altered Organelle Specificity 设计了具有改变细胞器特异性的nir - 1发射和选择性g -四重体DNA结合剂

IF 2.7 3区生物学

Biochemistry Biochemistry Pub Date : 2026-09-01 Epub Date: 2026-08-13 DOI: 10.1021/acs.biochem.6c00048

Sachin Metangle, Harikesh Kumar Gupta, Nabanita Das, Ratnesh Tiwari, Nihar Ranjan

{"title":"Designed NIR-I Emissive and Selective G-Quadruplex DNA Binder with Altered Organelle Specificity","authors":"Sachin Metangle, Harikesh Kumar Gupta, Nabanita Das, Ratnesh Tiwari, Nihar Ranjan","doi":"10.1021/acs.biochem.6c00048","DOIUrl":"https://doi.org/10.1021/acs.biochem.6c00048","url":null,"abstract":"In this work, we report the discovery of a G-quadruplexDNA-selectiveand near-infrared (NIR-I) emissive G-quadruplex binder derived froma known styryl-quinolinium-based compound. This molecule is uniquein its class, with an emission wavelength above 800 nm, and displaysselective G-quadruplex binding. Among the synthesized molecules, compound 2 emerged as a selective and the best G-quadruplex binderthrough comparative studies and exhibited strong thermal stabilizationon Pu22 G-quadruplex with a ΔTm of 21.7 °C (at a 1:3 DNA to ligand ratio). G-quadruplexDNA-binding studies showed that thermal stabilization was topology-dependent.CD, UV–vis, and docking studies were performed to confirm thebinding of these compounds to the different G-quadruplexes. SolutionNMR studies confirmed the binding of compound 2 to the Pu22 G-quadruplex DNA. Cell-based studies showed that compound 2 was significantly cytotoxic to MCF-7 cancer cells and wasreadily taken up by the cells. However, cell internalization studiesshowed contrasting changes in the internalization properties, withcompound 2 displaying a significant population on thenuclear periphery, which was altogether different from its parentcompound 1, which did not show such changes.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":"65 17","pages":"2699–2712"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148870323","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}

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Chemical Pathway–Dependent Structural Reorganization at a Hinge Microenvironment in the AcrA Adaptor Protein AcrA接头蛋白铰链微环境中依赖化学途径的结构重组

IF 2.7 3区生物学

Biochemistry Biochemistry Pub Date : 2026-09-01 Epub Date: 2026-08-21 DOI: 10.1021/acs.biochem.6c00276

Hermia Ip

{"title":"Chemical Pathway–Dependent Structural Reorganization at a Hinge Microenvironment in the AcrA Adaptor Protein","authors":"Hermia Ip","doi":"10.1021/acs.biochem.6c00276","DOIUrl":"https://doi.org/10.1021/acs.biochem.6c00276","url":null,"abstract":"Adaptor protein AcrA plays a centralrole in the assembly and functionof tripartite multidrug efflux pumps in Gram-negative bacteria, yethow its structural organization responds to coupled chemical perturbationsrather than solely to equilibrium conditions remains unclear. Residuesnear His285 define a hinge microenvironment linking the lipoyl andβ-barrel domains, suggesting a site for chemically sensitivestructural modulation. Here, site-directed spin labeling combinedwith continuous-wave electron paramagnetic resonance spectroscopywas used to examine AcrA under an Mg2+-driven perturbationthat simultaneously alters proton availability. Mg2+ additionproduced spectral broadening at residue 62 that was fully reversedby spin dilution, indicating increased interspin proximity withoutchanges in intrinsic side-chain dynamics. In contrast, direct acidificationto a comparable bulk pH in the absence of Mg2+ did notreproduce this behavior. Structural mapping places residue 62 in proximityto the His285-centered hinge region, suggesting that coupled changesin protonation and metal coordination bias local interaction networksand modulate interdomain organization. These findings demonstratethat equivalent bulk conditions can mask distinct molecular statesand identify chemical pathways as an important determinant of AcrAstructural dynamics.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":"65 17","pages":"2728–2735"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148861378","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

Improved Protein Semi-Synthesis Enables Biophysical Studies of Thioamide Destabilization of β-Sheet Interactions 改进的蛋白质半合成使β-薄片相互作用的硫酰胺不稳定的生物物理研究成为可能

IF 2.7 3区生物学

Biochemistry Biochemistry Pub Date : 2026-09-01 Epub Date: 2026-08-19 DOI: 10.1021/acs.biochem.6c00371

Evan S. K. Yanagawa, Kristen E. Fiore, Denver Y. Francis, Aiden Lesneski, Yanan Chang, Benjamin W. Roose, David W. Christianson, Kohei Sato, E. James Petersson

{"title":"Improved Protein Semi-Synthesis Enables Biophysical Studies of Thioamide Destabilization of β-Sheet Interactions","authors":"Evan S. K. Yanagawa, Kristen E. Fiore, Denver Y. Francis, Aiden Lesneski, Yanan Chang, Benjamin W. Roose, David W. Christianson, Kohei Sato, E. James Petersson","doi":"10.1021/acs.biochem.6c00371","DOIUrl":"https://doi.org/10.1021/acs.biochem.6c00371","url":null,"abstract":"Thioamides are naturalpost-translational modificationsof thepeptide backbone and can be introduced synthetically to probe proteinfolding or functionalize peptides for translational applications.In this work, we demonstrate that thioamide-containing peptides withC-terminal thioesters can be efficiently generated using Knorr pyrazoleactivation and used in subsequent native chemical ligation reactionsto generate thioamide-containing proteins. We compare this methodto acyl azide activation and find that both routes provide similaryields. We also investigate ultrasound-mediated desulfurization ofthe ligation site cysteine for potential advantages over chemicalradical initiators. Scaling up our syntheses allows us to study thioamideperturbations to the β-sheet region of the B1 domain of proteinG (GB1) as well as β-strand interactions in amyloid fibrilsof the Parkinson’s disease protein α-synuclein. In bothcontexts, we observe dramatic destabilization of the β-sheetnetworks, manifested in decreased GB1 thermal stability and alteredfolding and slowed aggregation of α-synuclein. These findingsillustrate the impact that a single atom substitution can have oncooperative hydrogen-bonding networks and prompt future study of bothsystems.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":"65 17","pages":"2736–2746"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148870483","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

Creating New Access Points for Strategic Synthase Engineering: Ethane Thioester Analogs as Truncated Coenzyme A Building Blocks Unlock Expanded Acyl Carrier Protein Loading Capabilities 为战略合成酶工程创造新的接入点：乙烷硫酯类似物作为截断辅酶A构建块解锁扩展酰基载体蛋白装载能力

IF 2.7 3区生物学

Biochemistry Biochemistry Pub Date : 2026-09-01 Epub Date: 2026-08-15 DOI: 10.1021/acs.biochem.6c00474

Jana C. Bowler, Anna-Lee C. Thompson, Colby M. Freeman, Yarra L. Ellett, Leah M. Seebald, Louise K. Charkoudian

{"title":"Creating New Access Points for Strategic Synthase Engineering: Ethane Thioester Analogs as Truncated Coenzyme A Building Blocks Unlock Expanded Acyl Carrier Protein Loading Capabilities","authors":"Jana C. Bowler, Anna-Lee C. Thompson, Colby M. Freeman, Yarra L. Ellett, Leah M. Seebald, Louise K. Charkoudian","doi":"10.1021/acs.biochem.6c00474","DOIUrl":"https://doi.org/10.1021/acs.biochem.6c00474","url":null,"abstract":"Strategic engineering of natural product biosyntheticpathwaysthrough the incorporation of alternative, tunable carbon-based buildingblocks represents a promising approach for accessing medicinally relevantmolecules. However, efforts toward this goal have been hindered bythe substrate specificity of component enzymes. In type I and typeII fatty acid synthases (FASs) and polyketide synthases (PKSs), theacyltransferase (AT) selects a specific malonyl-based coenzyme A (CoA)building block and transfers it onto the acyl carrier protein (ACP)for subsequent processing. Inspired by the observation that some ACPscan bypass the AT and “self-acylate”, we herein exploredthe tolerance of FAS and PKS ACPs to load both a variety of CoA substratesand ethane thioester (ET) analogs serving as truncated CoA buildingblocks. We observe that the Escherichia coli (E. coli) AT, FabD, can load and transfer methylmalonyl-CoA(mm-CoA) and malonyl-CoA (m-CoA) onto three ACPs: the type II Streptomyces coelicolor actinorhodin PKS ACP (ActACP), the E. coli type II FAS ACP (AcpP), and the type I Saccharopolyspora erythraea 6-deoxyerythronolide B PKS ACP6 (DEBS ACP6). SynthesizedET analogs of mm-CoA and m-CoA were loaded onto all three ACPs throughFabD-assisted acylation. Additionally, both in the presence and absenceof FabD, ACPs could be acylated with ET analogs of fluoromalonyl-,succinyl-, and glutaryl- building blocks. Overall, this work pushesthe limits of ACP substrate loading, revealing new complexity in carbon-basedbuilding block selection and establishing foundations for novel routestoward diverse functional group incorporation in FAS/PKS biosyntheticpathways.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":"65 17","pages":"2656–2660"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148861392","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

Adductome-Based Identification of Novel Oxidized Phospholipid-Lysine Adducts Formed in Low-Density Lipoprotein 基于内合体的低密度脂蛋白中新型氧化磷脂-赖氨酸加合物的鉴定

IF 2.7 3区生物学

Biochemistry Biochemistry Pub Date : 2026-09-01 Epub Date: 2026-08-13 DOI: 10.1021/acs.biochem.6c00425

Fumie Nakashima, Yuto Otsuka, Takuo Aoyama, Naoya Hirade, Haruka Sei, Hiroyuki Hattori, Ryosuke Kikuchi, Tadashi Matsushita, Ken-Ichi Yamada, Koji Uchida, Takahiro Shibata

{"title":"Adductome-Based Identification of Novel Oxidized Phospholipid-Lysine Adducts Formed in Low-Density Lipoprotein","authors":"Fumie Nakashima, Yuto Otsuka, Takuo Aoyama, Naoya Hirade, Haruka Sei, Hiroyuki Hattori, Ryosuke Kikuchi, Tadashi Matsushita, Ken-Ichi Yamada, Koji Uchida, Takahiro Shibata","doi":"10.1021/acs.biochem.6c00425","DOIUrl":"https://doi.org/10.1021/acs.biochem.6c00425","url":null,"abstract":"Theoxidative modification of low-density lipoprotein (LDL) isinvolved in the generation of lipid peroxidation-derived electrophilicaldehydes, which covalently react with apolipoprotein B-100 to formvarious adducts. Although the oxidative modification of LDL is criticalin the pathogenesis of atherosclerosis, the structural propertiesof adducts in oxidized LDL (oxLDL) remain unclear. Thus, we aimedto characterize oxLDL using the adductome approach, a comprehensivemass spectrometry-based analysis designed to detect specific productions from positively ionized oxidized phosphatidylcholine (oxPC) adducts.The amounts of several adducts, including four major oxPC-lysine (oxPC-Lys)adducts, prominently increased when LDL was oxidized with Cu2+. Analysis of the synthetic adduct candidates through mass spectrometryrevealed two oxPC-Lys Schiff base adducts and two novel oxPC-Lys amide-typeadducts as the major lysine adducts in oxLDL. The oxPC-Lys Schiffbase adducts could be transformed into stable amide-type adducts duringLDL oxidation. The amounts of oxPC-Lys adducts were significantlyhigher in the sera of hyperlipidemic mice than in the sera of controlmice. The recognition of oxPC-Lys adducts by macrophages suggestedthat these adducts were involved in the phagocytosis of oxLDL by macrophages.These findings provide insights into the structural properties oflipoproteins modified under oxidative stress and their biologicalimplications. Moreover, this study is the first to identify and quantifyoxPC-Lys amide-type adducts in vitro and in vivo.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":"65 17","pages":"2689–2698"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148870291","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