Biochemistry Biochemistry最新文献_第5页

The Long Splice Variant of Ribosomal Protein S24 Protects Cells from Stress and Is Induced by AMPK-ULK1-Regulated Autophagy Independent of mTORC1 核糖体蛋白S24的长剪接变体保护细胞免受应激，并由ampk - ulk1调节的独立于mTORC1的自噬诱导

IF 2.7 3区生物学

Biochemistry Biochemistry Pub Date : 2026-09-15 Epub Date: 2026-09-03 DOI: 10.1021/acs.biochem.6c00572

Runqi Qian, Jenna Goodbrand, Shannon N. Adams, Erin Trella, James Uniacke

{"title":"The Long Splice Variant of Ribosomal Protein S24 Protects Cells from Stress and Is Induced by AMPK-ULK1-Regulated Autophagy Independent of mTORC1","authors":"Runqi Qian, Jenna Goodbrand, Shannon N. Adams, Erin Trella, James Uniacke","doi":"10.1021/acs.biochem.6c00572","DOIUrl":"https://doi.org/10.1021/acs.biochem.6c00572","url":null,"abstract":"All living organisms have developed complex mechanismsto detectand react to environmental changes to maintain internal balance andsupport survival. One strategy that cells employ to respond to stressis to refocus the translation machinery to express select stress responseproteins, this includes the emerging field of specialized ribosomes.We have previously shown that a long splice variant of ribosomal proteinS24 (RPS24L) is induced by several fold in hypoxic monolayers andspheroids in several human cell lines in an autophagy-dependent manner.Here, we show that an allosteric activator of AMPK is sufficient toinduce RPS24L and autophagy in normoxia in an ULK1-dependent, butmTORC1-independent manner. Overexpression of RPS24L protected cellsfrom serum starvation and hypoxia, while RPS24 short isoform overexpressionduring stress impaired autophagy and the ability for cells to surviverelative to controls. We show that SRSF1 interacts with RPS24 mRNAand its autophagy-dependent decrease shifts splicing toward the RPS24Lvariant. This study provides new insights into the signaling and mechanismsthat regulate a ribosomal protein splice isoform that protects cellsfrom stress and that has been previously linked to cancer progression.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":"65 18","pages":"2916–2927"},"PeriodicalIF":2.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148974286","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

Factors Influencing the Selection of α-Amino Acids over β-Amino Acids in Nature: Studies Involving Protein-l-isoaspartyl Methyltransferase Substrates and Related Peptides 影响自然界α-氨基酸对β-氨基酸选择的因素：涉及蛋白质-l-异天冬氨酸甲基转移酶底物和相关肽的研究。

IF 2.7 3区生物学

Biochemistry Biochemistry Pub Date : 2026-09-15 Epub Date: 2026-08-28 DOI: 10.1021/acs.biochem.6c00401

Tanaya Chatterjee, Debarati Paul, Shubhra Ghosh Dastidar, Pinak Chakrabarti

{"title":"Factors Influencing the Selection of α-Amino Acids over β-Amino Acids in Nature: Studies Involving Protein-l-isoaspartyl Methyltransferase Substrates and Related Peptides","authors":"Tanaya Chatterjee, Debarati Paul, Shubhra Ghosh Dastidar, Pinak Chakrabarti","doi":"10.1021/acs.biochem.6c00401","DOIUrl":"10.1021/acs.biochem.6c00401","url":null,"abstract":"Tounderstand the differences resulting from the presence of anα- or β-amino acid in a peptide, we used two sets of aminoacids corresponding to Asp/isoAsp and Ala/isoAla in two types of hostpeptides: one containing Gly (with no side chains) and the other containingAla (representing amino acids with side chains), and measured theirtendency to form fibrils. The peptides with a β-amino acid formedfibrils, while those with an α-amino acid did not exhibit thisproclivity, as inferred from the thioflavin T (ThT) fluorescence intensitymeasurements. The fibrillation of the hexapeptide with isoAsp (theβ-amino acid corresponding to Asp) was inhibited by protein-l-isoaspartyl methyltransferase (PIMT), a repair enzyme thatconverts the abnormal isoAsp residue to normal Asp. Isothermal TitrationCalorimetry revealed the exothermic mode of binding of A6-isoAsp (Ala-basedhost hexapeptide) with PIMT. Far-UV CD spectroscopy revealed a β-sheetto α-helix transformation of isoAsp-containing peptides in thepresence of PIMT. The hydrophobicity of the peptides was measuredby noting their distribution in a mixture of water and octanol, wherethe β-amino acid exhibits a more positive hydrophobicity valuethan the α-amino acid. This may suggest that the hydrophobicforces bring chains containing β-amino acids together to enablenucleation for fibril formation. Molecular dynamics (MD) simulationsindicated that isoAsp-based host peptides, formed into fibrils, havestable structures over the course of simulations, whereas the equivalentpeptide with Asp disintegrated. Models of a single β-strandof these peptides bound to the active site of the enzyme were stable.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":"65 18","pages":"2885–2895"},"PeriodicalIF":2.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872300","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

Bioremediation of PET Pollution Using Microorganisms Active at Moderate Temperatures 中温活性微生物对PET污染的生物修复

IF 2.7 3区生物学

Biochemistry Biochemistry Pub Date : 2026-09-15 Epub Date: 2026-08-24 DOI: 10.1021/acs.biochem.6c00457

Kohei Oda, Alexander Wlodawer

{"title":"Bioremediation of PET Pollution Using Microorganisms Active at Moderate Temperatures","authors":"Kohei Oda, Alexander Wlodawer","doi":"10.1021/acs.biochem.6c00457","DOIUrl":"https://doi.org/10.1021/acs.biochem.6c00457","url":null,"abstract":"Plastics such as polyethylene terephthalate (PET) arewidely usedworldwide because they are inexpensive, versatile, and suitable fornumerous applications. However, most products made of PET are designedfor single use, and the resulting waste is chemically inert and highlyresistant to microbial degradation. Consequently, PET accumulationhas become a major source of environmental pollution and poses seriousthreats to ecosystems. Biorecycling and bioupcycling have emergedas some of the most promising strategies for reducing PET pollution.For macro-scale PET waste, industrial approaches are being developed,including those pursued by the French company Carbios, although significanttechnical and economic challenges remain. In contrast, for micro-and nanosized PET particles, commonly referred to as microplastics,no large-scale remediation systems have been implemented yet. Herewe highlight the potential applications of microorganisms and theirenzymes for remediation of microplastic pollution, especially becausethese systems can function at moderate temperatures, in contrast tohigh-temperature industrial processes. In particular, we highlightthe potential of utilizing the Ideonella sakaiensis system that was discovered a decade ago. PET-degrading enzymes encodedby this bacterium, such as IsPETase and IsMHEtase, are able to operate at moderate temperatures, unlike mostother enzymes being developed to provide bioremediation of PET pollution.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":"65 18","pages":"2809–2819"},"PeriodicalIF":2.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964621","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

The Spatiotemporal Regulation of Glucose Metabolism in Hematopoietic Stem Cells 造血干细胞糖代谢的时空调控

IF 2.7 3区生物学

Biochemistry Biochemistry Pub Date : 2026-09-15 Epub Date: 2026-09-01 DOI: 10.1021/acs.biochem.6c00155

Aoxue Wang, Yaqiong Chen, Hailing Li, Zhuo Zhang, Yuzheng Zhao

{"title":"The Spatiotemporal Regulation of Glucose Metabolism in Hematopoietic Stem Cells","authors":"Aoxue Wang, Yaqiong Chen, Hailing Li, Zhuo Zhang, Yuzheng Zhao","doi":"10.1021/acs.biochem.6c00155","DOIUrl":"https://doi.org/10.1021/acs.biochem.6c00155","url":null,"abstract":"Hematopoietic stem cell fate decisions are tightly coupledto dynamicchanges in glucose metabolism, which are precisely orchestrated acrossboth the spatial and temporal dimensions during differentiation. Trackingthe metabolic dynamics is crucial for understanding fate decisionsof hematopoietic stem cells and facilitating their efficient expansionfor therapeutic applications. Genetically encoded fluorescent biosensorshave emerged as powerful tools to monitor glucose metabolism in livinghematopoietic stem and precursor cells with high spatiotemporal resolution,enabling the in situ, real-time analysis of cellular metabolic heterogeneityat single-cell resolution and the analysis of the regulatory mechanismsunderlying hematopoietic functions. The insights revealed by biosensorsare often difficult to attain with conventional bulk or end pointassays. This review underscores the unique advantages and growingpromise of genetically encoded sensors in decoding the metabolic regulationof HSC differentiation, while critically examining current challengestoward their broader application in stem cell biology.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":"65 18","pages":"2785–2797"},"PeriodicalIF":2.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964558","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

Deciphering Structural Stabilities of Pre-messenger RNA Splicing Protein Dib1 Paralogs from Cyanidioschyzon merolae 紫顶藻前信使RNA剪接蛋白Dib1的结构稳定性分析

IF 2.7 3区生物学

Biochemistry Biochemistry Pub Date : 2026-09-15 Epub Date: 2026-08-28 DOI: 10.1021/acs.biochem.6c00536

Kathryn Wheeler, Bryce Dye, Vikram Kollipara, Corina Maeder

{"title":"Deciphering Structural Stabilities of Pre-messenger RNA Splicing Protein Dib1 Paralogs from Cyanidioschyzon merolae","authors":"Kathryn Wheeler, Bryce Dye, Vikram Kollipara, Corina Maeder","doi":"10.1021/acs.biochem.6c00536","DOIUrl":"https://doi.org/10.1021/acs.biochem.6c00536","url":null,"abstract":"Pre-messenger RNA (pre-mRNA) splicing is facilitatedby the spliceosome,a dynamic, multimegadalton ribonucleoprotein complex that catalyzesthe removal of intronic sequences from pre-mRNA. Dib1 is a small,essential U5-associated protein located in the catalytic core of thecanonical precatalytic spliceosome. Departure of Dib1 from the spliceosomeis necessary for the transition to a catalytically active spliceosome.Dib1 is highly conserved, including its presence as one of only ∼50core splicing proteins in the extremophile red alga Cyanidioschyzon merolae. Furthermore, two paralogsof Dib1 have been identified in the C. merolae genome. To understand the nature of the two C. merolae Dib1 paralogs, this study presents their biochemical characterization.Here, we determine the free energy of unfolding of both C. merolae Dib1 proteins, finding that despite sharing∼97% sequence identity, the stabilities of the two paralogsdiffer substantially. Additionally, only one C. merolae Dib1 paralog displayed a pH-dependent stabilization. Through mutationalanalysis, we identified two critical residues involved in the stabilitydifference between these paralogs and propose a structural explanationfor the observed difference. The collective differences in stabilityand pH dependence of the two C. merolae Dib1 paralogs suggest that the paralogs may play distinct roleswithin the C. merolae spliceosome orfunction under different cellular and environmental conditions. Theimportance of these findings stems beyond the spliceosome as theyinform on how a small number of residue changes in a protein can havea large impact on protein stability.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":"65 18","pages":"2865–2874"},"PeriodicalIF":2.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964600","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

Comparative Simulations of Conformational Flexibility during Radical Transport in Ribonucleotide Reductase 核糖核苷酸还原酶自由基转移过程中构象灵活性的比较模拟

IF 2.7 3区生物学

Biochemistry Biochemistry Pub Date : 2026-09-15 Epub Date: 2026-08-25 DOI: 10.1021/acs.biochem.6c00487

Matthew Tremblay, Sharon Hammes-Schiffer

{"title":"Comparative Simulations of Conformational Flexibility during Radical Transport in Ribonucleotide Reductase","authors":"Matthew Tremblay, Sharon Hammes-Schiffer","doi":"10.1021/acs.biochem.6c00487","DOIUrl":"https://doi.org/10.1021/acs.biochem.6c00487","url":null,"abstract":"Ribonucleotide reductase (RNR) is an essential enzymethat convertsribonucleotides to deoxyribonucleotides, utilizing a ∼32 Åchain of proton-coupled electron transfer (PCET) reactions spanningtwo protein subunits to generate a catalytic cysteine radical. Twocryogenic electron microscopy structures of the active complex of E. coli RNR are currently available. One structurewas trapped in the preturnover state, prior to radical translocation,and the other structure was trapped in the midturnover state, withthe radical in the active site. Herein, we use molecular dynamicssimulations to investigate the differences in hydrogen-bonding interactionsand conformational motions between the preturnover and midturnoverstates. Our simulations show that Y731, an interfacial tyrosine thatparticipates in the PCET pathway, samples multiple conformations inboth states, allowing it to participate in forward and reverse PCETbetween subunits. We also observe interfacial water channels betweenthe protein subunits in both states. Moreover, our simulations showthat E623, which is near Y730 in the preturnover structure and wasshown by previous simulations to mediate PCET between Y731 and Y730,can also sample conformations distal to Y730 in the preturnover state,similar to its position in the midturnover structure. Our mixed quantummechanical/molecular mechanical free energy simulations indicate thatforward radical transfer from Y731 to Y730 is thermodynamically favorablewith a reasonable free energy barrier, even in the absence of mediationby E623. These results provide insights into the critical role ofconformational motions and flexibility in regulating PCET reactionsat and near the protein subunit interface of RNR.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":"65 18","pages":"2896–2904"},"PeriodicalIF":2.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964606","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

Structures and Dynamics of Metabolites in Desiccation-Tolerant S. lepidophylla Plant Whole Cells Investigated by 13C Solid-State NMR 利用13C固体核磁共振研究耐干燥鳞茎植物全细胞代谢产物的结构和动态

IF 2.7 3区生物学

Biochemistry Biochemistry Pub Date : 2026-09-15 Epub Date: 2026-08-24 DOI: 10.1021/acs.biochem.6c00400

Yanina Pankratova, Mei Hong

{"title":"Structures and Dynamics of Metabolites in Desiccation-Tolerant S. lepidophylla Plant Whole Cells Investigated by 13C Solid-State NMR","authors":"Yanina Pankratova, Mei Hong","doi":"10.1021/acs.biochem.6c00400","DOIUrl":"https://doi.org/10.1021/acs.biochem.6c00400","url":null,"abstract":"A small fraction of vascular plants has evolved the remarkableability for their vegetative tissues to survive the loss of the vastmajority of water and revive upon rehydration. Understanding the chemicaland structural mechanisms for this desiccation tolerance is importantfor improving agricultural crop productivity in our changing climate.Although gas chromatography–mass spectrometry has been usedto profile metabolites in desiccation-tolerant plants, these studiesinvolve chemical extraction and hence do not provide quantitativeinformation about insoluble species in whole plants. Here, we employsolid-state NMR spectroscopy to examine the intact leaves and stemsof Selaginella lepidophylla, a well-knownresurrection plant, in the hydrated resurrected state and the drydormant state. Using rigid-selective 13C cross-polarization(CP), dynamic-selective 13C insensitive-nuclei-enhancement-by-polarizationtransfer (INEPT), and direct polarization 13C NMR experiments,we show that the dormant state of S. lepidophylla contains higher concentrations of dynamic lipids, most likely triglycerides,as well as higher levels of immobilized trehalose and other carbohydratescompared to the hydrated state. Two control plants that are desiccation-sensitivelack the high level of dynamic lipids, and the lipids that are presenthave distinct chemical shifts from those of S. lepidophylla. These results indicate that dynamic lipids play a significant rolein the adaptive response of vascular plants to severe water loss.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":"65 18","pages":"2875–2884"},"PeriodicalIF":2.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964622","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

Thermodynamic and Allosteric Drivers of Stilbene-Mediated Noncompetitive Inhibition of Firefly Luciferase 二苯乙烯介导的萤火虫荧光素酶非竞争性抑制的热力学和变构驱动因素。

IF 2.7 3区生物学

Biochemistry Biochemistry Pub Date : 2026-09-01 Epub Date: 2026-06-24 DOI: 10.1021/acs.biochem.6c00141

Adwaita SR Nair, Kunal Dhankhar, Anirban Das, Arup Samanta, Saugata Hazra

{"title":"Thermodynamic and Allosteric Drivers of Stilbene-Mediated Noncompetitive Inhibition of Firefly Luciferase","authors":"Adwaita SR Nair, Kunal Dhankhar, Anirban Das, Arup Samanta, Saugata Hazra","doi":"10.1021/acs.biochem.6c00141","DOIUrl":"10.1021/acs.biochem.6c00141","url":null,"abstract":"Photinus pyralis luciferase(Ppyluci) is widely used as a reporter molecule in high-throughput assaysfor biochemical, cell viability, and cellular pathway studies. Resveratrolis a naturally occurring stilbene compound known to inhibit luminescenceemission catalyzed by Ppy luci. Although it has been identified asan inhibitor, its detailed mechanism has not been investigated. Inthe present work, three stilbene compounds (piceatannol, resveratrol,and pterostilbene) were studied for their luminescence inhibitionproperties to determine the factors underlying inhibition and therole of functionalization. QSAR analysis, followed by steady-statekinetics, suggested an allosteric mode of inhibition by stilbene inhibitors,with piceatannol showing the highest potency. Isothermal titrationcalorimetry, docking, and MMPBSA/MMGBSA supported the inhibition assay,wherein the piceatannol have a higher binding affinity compared topterostilbene, driven by enthalpic contributions. In contrast, themelting temperature (Tm) comparison showed that resveratrol causesa higher shift in the global protein conformation despite having reducedinteractions with binding site residues. Stability studies using moleculardynamics simulation also highlighted a greater effect of resveratrolon global conformational stability compared to piceatannol. Densityfunctional theory (DFT) analysis indicated higher reactivity of piceatannol,underscoring its ability to hinder the oxidative microenvironmentto a greater extent and its inhibition potency. The study indicatethat stilbene inhibition is the result of a synergistic effect ofenthalpic contributions, localized allosteric perturbations, and changesin the oxidative microenvironment and is less dependent on globalconformational effects. Overall, this study highlights the importanceof carefully evaluating functionalization-driven, multifactorial inhibitionto mitigate assay artifacts.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":"65 17","pages":"2713–2727"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306250","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

Mechanistic Characterization of GedF Reveals a Ser–Tyr Catalytic Core with a Flexible Basic Residue in a Filamentous Fungal Anthraquinone SDR 丝状真菌蒽醌SDR中具有柔性碱基残基的Ser-Tyr催化核的GedF机理表征

IF 2.7 3区生物学

Biochemistry Biochemistry Pub Date : 2026-09-01 Epub Date: 2026-08-12 DOI: 10.1021/acs.biochem.6c00266

Ning Xu, Yongsong Wu, Dan Liu, Keke Zhang, Danni Wu, Siyu Du, Xuenian Huang, Xuefeng Lu, Honglei Ma, Feifei Qi

{"title":"Mechanistic Characterization of GedF Reveals a Ser–Tyr Catalytic Core with a Flexible Basic Residue in a Filamentous Fungal Anthraquinone SDR","authors":"Ning Xu, Yongsong Wu, Dan Liu, Keke Zhang, Danni Wu, Siyu Du, Xuenian Huang, Xuefeng Lu, Honglei Ma, Feifei Qi","doi":"10.1021/acs.biochem.6c00266","DOIUrl":"https://doi.org/10.1021/acs.biochem.6c00266","url":null,"abstract":"Thecleavage of the C10–C4a bond in anthraquinones is akey step in generating ring-opened quinone derivatives in filamentousfungi. GedF, a short-chain dehydrogenase/reductase (SDR) from Aspergillus terreus, together with the dioxygenaseGedK, mediates this transformation, yet the enzymatic mechanism ofGedF remains unclear. Here, isotope labeling experiments confirm thatreduction of Questin-to-Questin hydroquinone incorporates one protonfrom NADPH and one from water. Structural modeling, molecular docking,and site-directed mutagenesis reveal that GedF employs a noncanonicalcatalytic architecture featuring a conserved Ser–Tyr catalyticcore instead of the classical Asn-Ser-Tyr-Lys tetrad typical of SDRs.Notably, mutagenesis and comparative analysis indicate that a positivelycharged residue is required for catalysis but is not strictly position-conserved,consistent with a role in maintaining the catalytic microenvironmentand facilitating proton transfer. Phylogenetic and sequence analysesshow that GedF belongs to the NAD(P)H-dependent SDR clade, and thatvariation in the positioning of basic residues occurs among homologueswhile preserving the conserved Ser–Tyr catalytic core. Thesefindings elucidate the catalytic mechanism of GedF and uncover analternative SDR catalytic strategy involved in anthraquinone ring-openingbiosynthesis in filamentous fungi.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":"65 17","pages":"2679–2688"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148870351","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

Serine: From Metabolic Intermediate to Signaling Entity 丝氨酸：从代谢中间体到信号实体

IF 2.7 3区生物学

Biochemistry Biochemistry Pub Date : 2026-09-01 Epub Date: 2026-08-11 DOI: 10.1021/acs.biochem.6c00353

Sharon Spizzichino, Giovanni Maria Varchetta, Giulia Elizabeth Borsatti, Emma Chillemi, Marzia Arese, Alessio Paone, Serena Rinaldo, Francesca Cutruzzolà

{"title":"Serine: From Metabolic Intermediate to Signaling Entity","authors":"Sharon Spizzichino, Giovanni Maria Varchetta, Giulia Elizabeth Borsatti, Emma Chillemi, Marzia Arese, Alessio Paone, Serena Rinaldo, Francesca Cutruzzolà","doi":"10.1021/acs.biochem.6c00353","DOIUrl":"https://doi.org/10.1021/acs.biochem.6c00353","url":null,"abstract":"Serine, a nonessential amino acid classically definedas a precursorfor protein synthesis and one-carbon metabolism, is increasingly recognizedas a signaling metabolite that links the cellular metabolic statusto regulatory decision-making. Intracellular serine availability isshaped by nutrient conditions, glycolytic flux, and activity of theserine synthesis pathway, and these fluctuations are sensed to elicitcoordinated metabolic and signaling responses. This review discussesmechanisms by which serine modulates cell growth and stress responses,with particular emphasis on its interaction with central nutrient-sensingpathways, including mTORC1 and the integrated stress response. Inparallel, serine-driven one-carbon metabolism is examined for itsrole in supporting nucleotide biosynthesis, methylation reactions,and redox homeostasis through folate-dependent pathways and NADPHgeneration, thereby coupling anabolic processes to the maintenanceof redox balance and genome integrity. In addition to intracellularfunctions, serine contributes to intercellular signaling. Conversionof l-serine to d-serine mediates neuromodulatoryactivity via N-methyl-d-aspartate receptors,while serine availability also influences immune cell function, inflammatorysignaling, and host–microbe interactions. Dysregulation ofserine metabolism and signaling is further considered in the contextof disease states, including cancer, neurodegeneration, and metabolicdisorders. Together, these observations support a framework in whichserine functions as an information-bearing metabolic signal that coordinatesthe biosynthetic capacity with cellular adaptation and intercellularcommunication.","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":"65 17","pages":"2629–2643"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148870378","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