Journal of Inorganic Biochemistry最新文献

{"title":"Roles of biological heme-based sensors of O₂ in controlling bacterial behavior.","authors":"Florian J Fekete, Emily E Weinert","doi":"10.1016/j.jinorgbio.2025.113071","DOIUrl":"https://doi.org/10.1016/j.jinorgbio.2025.113071","url":null,"abstract":"<p><p>The heme cofactor is found across all domains of life, serving a variety of purposes, such as gas transport, catalysis of reactions, and gas sensing. Heme-based gas sensors bind NO, CO, and O₂, modulating cellular responses to these ligands. The widespread nature of heme proteins and the importance of oxygen to most life forms make them an intriguing system to investigate the role of heme proteins and bacterial oxygen response. Bacteria use various classes of heme sensors to detect oxygen signals, including heme-containing Per-Arnt-Sim (hPAS), and sensor globin domain-containing proteins. Globin coupled sensor (GCS) proteins have emerged as another widespread heme-based O₂ sensing protein family, providing insights into stabilization of O₂ binding and ligand-selective signaling. GCS proteins also are useful as models for intracellular cyclic-di-guanosine monophosphate (c-di-GMP) signaling, as the most extensively studied group of GCS proteins contain diguanylate cyclase (DGC) output domains, which synthesize c-di-GMP upon ligand binding. These proteins, such as Escherichia coli EcDosC (Direct Oxygen Sensor Cyclase), Pectobacterium carotovorum PccDgcO, and Bordetella pertussis BpeGReg, have been investigated regarding their heme characteristics, biochemistry, and roles in modulating bacterial response to O₂. In addition, the interaction between the E. coli hPAS protein DosP and the GCS DosC highlight the complex systems used to control downstream bacterial response to environmental oxygen.</p>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":" ","pages":"113071"},"PeriodicalIF":3.2,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145090972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Larry Que: Reflections from a life in science.","authors":"","doi":"10.1016/j.jinorgbio.2025.113069","DOIUrl":"https://doi.org/10.1016/j.jinorgbio.2025.113069","url":null,"abstract":"","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":" ","pages":"113069"},"PeriodicalIF":3.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Caffeic acid-Fe3+ nanohybrids loaded with berberine/baicalin for NIR-activated antibacterial therapy via ROS generation and photothermal effects","authors":"Meixuan Zhang ,&nbsp;Qin Zhang ,&nbsp;Xuemin Mu ,&nbsp;Xiaolin Wang ,&nbsp;Shuhui Zhang ,&nbsp;Wenyi Zhao ,&nbsp;Xiaoming Song ,&nbsp;Lulu Pan ,&nbsp;Yanyan Li","doi":"10.1016/j.jinorgbio.2025.113070","DOIUrl":"10.1016/j.jinorgbio.2025.113070","url":null,"abstract":"<div><div>The escalating threat of bacterial infections underscores the pressing need for innovative antibacterial solutions. In this study, BA-BBR@MPN nanoparticles (BA-BBR@MPN NPs) were synthesized through the self-assembly of berberine (BBR) and baicalin (BA), followed by modification with a metal-phenolic network (MPN) derived from caffeic acid and Fe³⁺. In the slightly acidic environment of the infected site, the MPN decomposes to release iron ions, BBR, and BA. The iron ions catalyze the generation of hydroxyl radicals (·OH) from hydrogen peroxide (H₂O₂), enabling chemodynamic therapy (CDT) while simultaneously depleting glutathione levels. When combined with 808 nm laser-induced photothermal therapy (PTT), the system demonstrates synergistic antibacterial effects. Both in vitro and in vivo studies confirmed the platform's broad-spectrum antibacterial activity against Gram-positive and Gram-negative bacteria, along with excellent biocompatibility and significant wound-healing promotion. This multifunctional nanoplatform represents a promising strategy for combating bacterial infections while simultaneously promoting tissue repair.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"274 ","pages":"Article 113070"},"PeriodicalIF":3.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145106368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preface Celebrating the career of Prof. Lawrence Que, Jr. on the occasion of his retirement from the University of Minnesota.","authors":"Michael J Maroney","doi":"10.1016/j.jinorgbio.2025.113068","DOIUrl":"https://doi.org/10.1016/j.jinorgbio.2025.113068","url":null,"abstract":"","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":" ","pages":"113068"},"PeriodicalIF":3.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying bacterial heme sensor protein interacting partners under varying oxygen tensions using proximity labeling","authors":"Florian J. Fekete,&nbsp;Emily E. Weinert","doi":"10.1016/j.jinorgbio.2025.113067","DOIUrl":"10.1016/j.jinorgbio.2025.113067","url":null,"abstract":"<div><div>Heme proteins play cellular roles in sensing and signaling, including reporting on labile heme pools and environmental gas/redox conditions. A major challenge in understanding these sensing pathways is the identification of proteins involved in the signaling cascade, as many of interactions are transient or low affinity. In addition, differences in oxygen levels or redox stress can alter cellular signaling, further complicating the analysis. Herein, a proximity labeling method (TurboID) is adapted for identifying proteins in proximity of the <em>E. coli</em> oxygen-sensing heme protein complex, DosC/P, which is involved in cyclic di-GMP metabolism, under aerobic and anaerobic conditions. These studies reveal oxygen-dependent differences in proteins in proximity of the DosC-DosP complex, which could result in differences in cellular behavior under aerobic and anaerobic conditions. Results identified glycine decarboxylase GcvP in proximity of DosCP and that GcvP binds <em>c</em>-di-GMP, revealing a potential new <em>c</em>-di-GMP signaling target and a novel role for the DosC-DosP complex in modulating aerobic one‑carbon metabolism. The application of proximity labeling developed in this work can be used not just for this oxygen-sensing complex, but can also be easily adapted to study the interactions of other heme proteins in bacteria.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"274 ","pages":"Article 113067"},"PeriodicalIF":3.2,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145046938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Key roles of GAPDH, Hsp90, and NO in heme trafficking","authors":"Dennis J. Stuehr ,&nbsp;Pranjal Biswas ,&nbsp;Yue Dai ,&nbsp;Dhanya Thamaraparambil Jayaram ,&nbsp;Priya Das Sinha ,&nbsp;Elizabeth A. Sweeny ,&nbsp;Arnab Ghosh","doi":"10.1016/j.jinorgbio.2025.113066","DOIUrl":"10.1016/j.jinorgbio.2025.113066","url":null,"abstract":"<div><div>Intracellular trafficking of mitochondrial heme to create functional heme proteins presents a fundamental challenge in animal cells. This article provides some background on heme allocation, discusses some of the concepts, and then reviews research from the last two decades that has uncovered unexpected and important roles for glyceraldehyde 3-phosphate dehydrogenase (GAPDH), heat shock protein 90 (Hsp90), and nitric oxide (NO) in enabling and regulating cell heme allocations to hemeproteins that mature and function outside of the mitochondria. A model for how hemeprotein heme contents and functions in cells can be regulated through the coordinate participation of GAPDH, Hsp90, and NO is presented.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"274 ","pages":"Article 113066"},"PeriodicalIF":3.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The thiolation of U34 at carbon 2 in tRNA by Escherichia coli MnmA precedes modification at carbon 5 and is dependent on a [4Fe-4S] cluster","authors":"Sylvain Gervason ,&nbsp;Sambuddha Sen ,&nbsp;Jingjing Zhou ,&nbsp;Karolina Podskoczyj ,&nbsp;Grazyna Leszczynska ,&nbsp;Sylvain Caillat ,&nbsp;Jean-Luc Ravanat ,&nbsp;Marc Fontecave ,&nbsp;Béatrice Golinelli-Pimpaneau","doi":"10.1016/j.jinorgbio.2025.113064","DOIUrl":"10.1016/j.jinorgbio.2025.113064","url":null,"abstract":"<div><div>Chemical modifications of transfer RNAs (tRNAs) fine-tune the recognition of messenger RNA codons on the ribosome for accurate protein translation. Uridine 34 (U34) of the anticodon of three tRNAs is modified in all domains of life. In bacteria, U34 is modified at C5 by aminomethyl derivatives by MnmE/MnmG enzymes and at C2 by a sulfur atom by MnmA enzymes from two distinct classes. C-type MnmAs possess a CXXC+ C catalytic motif, in which cysteines bind a [4Fe-4S] cluster essential for catalysis. D-type MnmAs possess a DXXC+ C catalytic motif, which can also bind a [4Fe-4S] cluster, but the function of the cluster is controversial. To shed light on the role of the [4Fe-4S] cluster in the thiolation reaction, we report here new <em>in vitro</em> catalytic assays of the D-type <em>Escherichia coli</em> MnmA enzyme (EcMnmA) before, and after cluster reconstitution under anaerobic conditions. We confirm that that only holo-EcMnmA can thiolate U34 in a tRNA transcript using sulfide as a sulfur source and show that 1) a bulk <em>E. coli</em> Δ<em>mnmA</em> tRNA, containing the C5 modification, is not a substrate, indicating that thiolation at C2 precedes modification at C5, 2) cysteine with IscS cannot provide the sulfur atom for tRNA thiolation without a reductant and 3) the variant, in which the aspartate of the DXXC + C motif is replaced by cysteine, is efficient in U34-tRNA thiolation <em>in vitro</em> but not <em>in vivo</em>, raising questions about the <em>in vivo</em> function of soft cluster coordination.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"274 ","pages":"Article 113064"},"PeriodicalIF":3.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photodynamic immunotherapy of Ruthenium(II) polypyridyl complexes: Application in the treatment of colorectal Cancer","authors":"Lin Zhou ,&nbsp;Huiyan Hu ,&nbsp;Jiongbang Li ,&nbsp;Yan Yang ,&nbsp;Shuang Tian ,&nbsp;Yajie Niu ,&nbsp;Yunjun Liu ,&nbsp;Xiandong Zeng","doi":"10.1016/j.jinorgbio.2025.113056","DOIUrl":"10.1016/j.jinorgbio.2025.113056","url":null,"abstract":"<div><div>In this study, a new ligand 2-(4-(1<em>H</em>-imidazol-1-yl)phenyl)-1<em>H</em>-imidazo[4,5-<em>f</em>][1,10]phenanthroline (IPIP) was synthesized and reacted with cis-[Ru(phen)₂Cl₂]·2H₂O and cis-[Ru(dip)₂Cl₂]·2H₂O to form two new Ru(II) complexes [Ru(phen)₂(IPIP)](PF₆)₂ (Ru1a) and [Ru(dip)₂(IPIP)](PF₆)₂ (Ru1b). The cytotoxicity of Ru1a and Ru1b against both cancer and normal cells was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The results revealed that Ru1a exhibits moderate and Ru1b shows no cytotoxic activity in the dark. However, after 1 h of irradiation, Ru1a exhibited significant cytotoxicity against HCT116 cells, while Ru1b still showed no cytotoxic activity toward the selected cancer cells. Further investigation via cell uptake, mitochondrial localization, mitochondrial membrane potential, cytochrome C release, and western blotting techniques confirmed that Ru1a induced apoptosis in HCT116 cells via the mitochondrial pathway. RNA-sequence assay showcases that Ru1a caused cell death through ferroptosis. The levels of lipid peroxidation product of malondialdehyde (MDA) were elevated, while the expression of GPX4 was reduced. These findings affirmed that Ru1a promotes cell death through ferroptosis. Antitumor in vivo confirmed that Ru1a exerts anticancer activity in the tumor microenvironment (TME) by inducing immunogenic cell death and activating immune responses to enhance CD8⁺ T cells, thereby directly killing colorectal cancer cells.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"274 ","pages":"Article 113056"},"PeriodicalIF":3.2,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145027351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of six novel dinuclear calcium(II) complexes based on 8-hydroxyquinoline as anticancer agents","authors":"Xiao-Mei Huang ,&nbsp;Yue Xu ,&nbsp;Si-Mei Qin ,&nbsp;Ming-Xiong Tan ,&nbsp;Qi-Pin Qin ,&nbsp;Tai-Ming Shao ,&nbsp;Hong Liang","doi":"10.1016/j.jinorgbio.2025.113055","DOIUrl":"10.1016/j.jinorgbio.2025.113055","url":null,"abstract":"<div><div>This study reports the synthesis and antitumor evaluation of six novel dinuclear calcium(II) complexes with the general formula [Ca₂(<em>μ</em>₂-O)₂(QM^x)₄(QH^y)₂], designated as <strong>CaQ1</strong> through <strong>CaQ6</strong>. These complexes incorporate various deprotonated 8-hydroxyquinoline ligands (H-QM¹−H-QM⁴) and 1,10-phenanthroline derivatives (QH²), synthesized using Ca(NO₃)₂·4H₂O. The specific compositions are as follows: <strong>CaQ1:</strong> H-QM¹ = 5,7-dibromo-8-hydroxyquinoline (x = 1), QH¹ = bathophenanthroline; <strong>CaQ2:</strong> H-QM² = 5,7-dichloro-8-quinolinol (x = 2), QH¹ = bathophenanthroline; <strong>CaQ3:</strong> H-QM³ = 5,7-diiodo-8-hydroxyquinoline (x = 3), QH² = 1,10-phenanthroline; <strong>CaQ4:</strong> H-QM² = 5,7-dichloro-8-quinolinol (x = 2), QH² = 1,10-phenanthroline; <strong>CaQ5:</strong> H-QM⁴ = clioquinol (x = 4), QH² = 1,10-phenanthroline; <strong>CaQ6:</strong> H-QM¹ = 5,7-dibromo-8-hydroxyquinoline (x = 1), QH² = 1,10-phenanthroline. Cytotoxicity was assessed using the cell counting kit-8 assay, and the results showed that <strong>CaQ1</strong>–<strong>CaQ6</strong> exhibited greater selectivity toward cisplatin-resistant SK-OV-3/DDP ovarian (cis-SK3) cancer cells compared to both nontumorigenic HL-7702 liver cells and parental SK-OV-3 ovarian cancer cells. Notably, <strong>CaQ1</strong> and <strong>CaQ2</strong>, which contain the active H-QM¹, H-QM², and QH¹ ligands, showed the most potent cytotoxicity, with IC₅₀ values of 3.59 ± 0.67 μM and 2.73 ± 0.25 μM, respectively, against cis-SK3 cells. Apoptosis induced by <strong>CaQ1</strong> and <strong>CaQ2</strong> was mediated by mitophagy activation and adenosine triphosphate depletion, with <strong>CaQ2</strong> being more effective than <strong>CaQ1</strong>—likely due to the presence of QM² and QH¹ ligands in the <strong>CaQ2</strong> complex. In conclusion, these findings suggest that the synthesized 8-hydroxyquinoline-based binuclear calcium(II)-1,10-phenanthroline complexes (<strong>CaQ1</strong>−<strong>CaQ6)</strong> represent promising Ca(II)-based anticancer drug candidates.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"274 ","pages":"Article 113055"},"PeriodicalIF":3.2,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical and functional effects of substituting coevolved residues from Ω-loop C of yeast Iso-1-cytochrome c into human cytochrome c","authors":"Ariel K. Frederick ,&nbsp;Bruce E. Bowler","doi":"10.1016/j.jinorgbio.2025.113053","DOIUrl":"10.1016/j.jinorgbio.2025.113053","url":null,"abstract":"<div><div>Omega loop C (residues 40–57) of cytochrome <em>c</em> (Cyt<em>c</em>) is a common location for naturally-occurring variants of human Cyt<em>c</em> that cause thrombocytopenia 4 (THC4). These variants are characterized by significant increases in the intrinsic peroxidase activity of Cyt<em>c</em>, which appears to be linked to increased dynamics in Ω-loop D (residues 71–85). The mutations in Ω-loop C enhance the dynamics of Ω-loop D by decreasing the acid dissociation constant of the trigger group (p<em>K</em>_H) of the alkaline conformational transition. The intrinsic peroxidase activity of human Cyt<em>c</em> is considerably lower than that of yeast iso-1-Cyt<em>c</em>. We identified three sites in or near Ω-loop C, which show evidence of coevolution and reasoned that they could play a role in minimizing the intrinsic peroxidase activity of human Cyt<em>c</em> so that this activity can be an effective switch in the early stages of apoptosis. We prepared T40S, I57V and T63N variants of human Cyt<em>c</em>, which substitute the amino acids found in iso-1-Cyt<em>c</em> into these sites. Studies on the global and local (alkaline transition) stabilities and peroxidase activities of these variants show modest effects. These results show that evolution of Ω-loop C has acted to preserve the dynamics of Ω-loops C and D, which surround the heme. Like the THC4 variants, the T40S and T63N variants show a significant decrease in the p<em>K</em>_H of the alkaline transition. However, unlike the THC4 variants this is coupled to changes in p<em>K</em>_C that disfavor the alkaline state, thereby leaving the intrinsic peroxidase activity unaffected.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"274 ","pages":"Article 113053"},"PeriodicalIF":3.2,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}