Journal of Biological Inorganic Chemistry最新文献

{"title":"Donut-shaped [NaP₅W₃₀O₁₁₀]^14- polyoxometalate as a promising antidiabetic drug-candidate: putative mechanisms of action.","authors":"Marko Dinčić, Mirjana B Čolović, Jasna Todorović, Neda Milinković, Branimir Radosavljević, Ali S Mougharbel, Ulrich Kortz, Danijela Z Krstić","doi":"10.1007/s00775-025-02098-w","DOIUrl":"https://doi.org/10.1007/s00775-025-02098-w","url":null,"abstract":"<p><p>The aim of this study was to elucidate the potential mechanism of the antihyperglycemic action of the donut-shaped Preyssler-Pope-Jeannin polyanion salt (NH₄)₁₄[NaP₅W₃₀O₁₁₀] 31H₂O (NaP₅W₃₀) and its effect on metabolic disorders associated with diabetes. For this purpose, relevant parameters of blood glucose regulation, lipid profile, and electrolyte status were monitored in streptozotocin (STZ)-induced diabetic rats that were orally treated with 20 mg/kg/day NaP₅W₃₀ for three weeks. The serum insulin concentration was increased in diabetic animals treated with NaP₅W₃₀ (20 mg/kg/day, per os, three weeks), which could be one of the possible mechanisms of the confirmed antihyperglycemic effect. In addition, the administration of NaP₅W₃₀ significantly reduced hyperglycemia and glycated haemoglobin A_1c (HbA_1c) in STZ-induced diabetic rats, although normoglycemic values were not achieved. Furthermore, a statistically significant 1.3-fold reduction in serum total cholesterol and a 1.7-fold reduction in high-density lipoprotein (HDL) cholesterol were observed in the NaP₅W₃₀ treatment group compared to the diabetic control group. In contrast, NaP₅W₃₀ had no effect on homeostasis model assessment of insulin resistance (HOMA-IR) index values, electrolyte concentrations, or serum concentrations of low-density lipoprotein (LDL) cholesterol, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), or total triglycerides. In summary, NaP₅W₃₀ effectively improved glycoregulation in diabetic rats via the considerable stimulation of insulin as a putative mechanism. Moreover, NaP₅W₃₀ did not affect rat weight or disrupt lipid and electrolyte status, common diabetes-followed side effects and risk factors for various life-threatening complications. Thus, NaP₅W₃₀ could be considered a promising antidiabetic drug-candidate that deserves further investigation.</p>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The activation of the metal-containing regulatory protein NiaR from Thermotoga maritima by its effector, nicotinic acid.","authors":"Wai Chung Dorothy Cheng, Yuxin Li, Maileen Nakashima, Pierre Moënne-Loccoz, Katherine W Rush, Arthur Glasfeld","doi":"10.1007/s00775-025-02096-y","DOIUrl":"https://doi.org/10.1007/s00775-025-02096-y","url":null,"abstract":"<p><p>NiaR is a regulatory protein that represses the expression of proteins involved in the de novo biosynthesis and uptake of nicotinic acid (NA), with NA acting as a co-repressor. The previously published structure of NiaR from Thermotoga maritima (TmNiaR) identified it as a functional homodimer containing a transition metal ion in a suspected NA-binding pocket. Here, we present the crystal structure of NA bound to the iron-metalated form of TmNiaR. Supported by spectroscopic and solution studies, this structure shows that NA binds to a protein-bound ferrous ion via its ring nitrogen. In addition, the carboxylate group on NA interacts with Tyr108 from the dyad-related subunit, repositioning the likely DNA-binding domains of the dimer to promote high-affinity interactions with DNA operators. The specificity of TmNiaR for NA can be explained by the hydrogen bonding scheme within the NA-binding pocket.</p>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A semisynthetic, multicofactor artificial metalloenzyme retains independent site activity.","authors":"Ashlee E Wertz, Ilmari Rosenkampff, Philippe Ibouanga, Matthias Huber, Corinna R Hess, Olaf Rüdiger, Hannah S Shafaat","doi":"10.1007/s00775-025-02095-z","DOIUrl":"https://doi.org/10.1007/s00775-025-02095-z","url":null,"abstract":"<p><p>Native metalloenzymes are unparalleled in their ability to perform efficient small molecule activation reactions, converting simple substrates into complex products. Most of these natural systems possess multiple metallocofactors to facilitate electron transfer or cascade catalysis. While the field of artificial metalloenzymes is growing at a rapid rate, examples of artificial enzymes that leverage two distinct cofactors remain scarce. In this work, we describe a new class of artificial enzymes containing two different metallocofactors, incorporated through bioorthogonal strategies. Nickel-substituted rubredoxin (Ni^Rd), which is a structural and functional mimic of [NiFe] hydrogenases, is used as a scaffold. Incorporation of a synthetic bimetallic inorganic complex based on a macrocyclic biquinazoline ligand (M^MBQ) was accomplished using a novel chelating thioether linker. Neither the structure of the Ni^Rd active site nor the M^MBQ were altered upon attachment, and each site retained independent redox activity. Electrocatalysis was observed from each site, with the switchability of the system demonstrated through the use of catalytically inert metal centers. This M^MBQ-Ni^Rd platform offers a new avenue to create multicofactor artificial metalloenzymes in a robust system that can be easily tuned both through modifications to the protein scaffold and the synthetic moiety, with applications for redox catalysis and tandem reactivity.</p>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iron-sulfur clusters: the road to room temperature.","authors":"Brighton A Skeel, Daniel L M Suess","doi":"10.1007/s00775-025-02094-0","DOIUrl":"https://doi.org/10.1007/s00775-025-02094-0","url":null,"abstract":"<p><p>Iron-sulfur proteins perform a wide variety of reactions central to the metabolisms of all living organisms. Foundational to their reaction chemistry are the rich electronic structures of their constituent Fe-S clusters, which differ in important ways from the active sites of mononuclear Fe enzymes. In this perspective, we summarize the essential electronic structure features that make Fe-S clusters unique, and point to the need for studies aimed at understanding the electronic basis for their reactivity under physiological conditions. Specifically, at ambient temperature, both the ground state and a large number of excited states are thermally populated, and thus a complete understanding of Fe-S cluster reactivity must take into account the properties, energies, and reactivity patterns of these excited states. We highlight prior research toward characterizing the low-energy excited states of Fe-S clusters that has established what is now a consensus model of these excited state manifolds and the bonding interactions that give rise to them. In particular, we discuss the low-energy alternate spin states and valence electron configurations that occur in Fe-S clusters of varying nuclearities, and finally suggest that there may be unrecognized functional roles for these states.</p>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitric oxide transfer between nominal Fe and Co biomimetics of the nitrile hydratase active site.","authors":"Sarnali Sanfui, Manish Jana, Nadia Small, Donald J Darensbourg, Marcetta Y Darensbourg","doi":"10.1007/s00775-024-02092-8","DOIUrl":"https://doi.org/10.1007/s00775-024-02092-8","url":null,"abstract":"<p><p>Related to the inactive form of nitrile hydratase, NHase, that contains Fe(NO) within tripeptide N₂S₂ binding environment, the NO transfer reactivity of (bis-mercaptoethane diazacycloheptane)Fe(NO) and (bis-mercaptoethane diazadimethylethane)Fe(NO) is compared to Co(NO) analogs. Acceptors of NO include cobalt octaethylporphyrin and the [(N₂S₂)M] dimeric precursors in the synthesis of the Fe(NO) and Co(NO) biomimetics. Qualitative rates are augmented by a definitive kinetic study finding that rates of NO transfer from (N₂S₂)M(NO) to [(N₂S₂)M']₂ are dependent on M and M' as well as the hydrocarbon N to N and N to S linkers. We conclude that while Fe(NO) and Co(NO) units are similar in chemical stability, minor first coordination sphere differences may favor the former, Fe(NO), consistent with the discovery of Fe(NO), but not Co(NO), in the as-isolated NHase active site.</p>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impacts of amino acid-linked platinum(II) complexes on DNA structure.","authors":"Deepak Shrestha, Bett Kimutai, Christine S Chow","doi":"10.1007/s00775-025-02097-x","DOIUrl":"https://doi.org/10.1007/s00775-025-02097-x","url":null,"abstract":"<p><p>The discovery of cisplatin (cisPt) as an effective anticancer agent was a milestone in the health industry. Despite its success, undesired side effects and acquired resistance still limit the therapeutic usefulness of cisPt. Intrastrand adduct formation at consecutive purines and structural modifications of DNA caused by platinum(II) complexes are important factors for antitumor efficacy. In this study, we examined amino acid-linked platinum(II) complexes, collectively referred to as AAPt, for antiproliferative activity and ability to induce DNA bending. The antiproliferative activity of one AAPt complex tested against a prostate cancer cell line was comparable to that of cisPt, whereas only activity of the AAPt complex was lower in a normal human prostate cell line. Various AAPt analogues were examined for impact on the structures of DNAs with four different purine dinucleotide target sites (GG, AG, GA, and AA) and compared to the parent cisPt. The roles of side-chain identity, chirality, and coordination type (e.g., (N,O) vs. (N,N)) of AAPt complexes are discussed with respect to DNA adduct formation and ability to induce DNA bending. Although the AAPt complexes display different nucleotide preferences (A for AAPt vs. G for cisPt), DNAs containing GG-platinum adducts display a greater degree of bending compared to DNAs with AA-platinum adducts.</p>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of lipid dynamics and permeability in styrene-maleic acid and diisobutylene-maleic acid copolymer lipid nanodiscs by electron paramagnetic resonance spectroscopy.","authors":"Andrew K Morris, Robert M McCarrick, Gary A Lorigan","doi":"10.1007/s00775-024-02091-9","DOIUrl":"https://doi.org/10.1007/s00775-024-02091-9","url":null,"abstract":"<p><p>Lipid nanoparticles formed with copolymers are a new and increasingly powerful tool for studying membrane proteins, but the extent to which these systems affect the physical properties of the membrane is not completely understood. This is critical to understanding the caveats of these new systems and screening for structural and functional artifacts that might be caused in the membrane proteins they are used to study. To better understand these potential effects, the fluid properties of dipalmitoylphosphatidylcholine lipid bilayers were examined by electron paramagnetic resonance (EPR) spectroscopy with spin-labeled reporter lipids in either liposomes or incorporated into nanoparticles with the copolymers diisobutylene-maleic acid or styrene maleic acid. Lineshape analysis at varying temperatures reveal a major change in the phase transition behavior of the lipids from a sharp melting curve in liposomes to a more gradual transition in nanoparticles. Electron spin echo envelope modulation (ESEEM) spectroscopy reveals changes in water permeability between mimetic systems, which is further supported by power-saturation measurements showing increased dequenching of spin lipids in diisobutylene-maleic acid nanoparticles compared to maleic acid nanoparticles. These results suggest that diisobutylene-maleic acid nanoparticles may have more physiological fluid properties than styrene-maleic acid nanoparticles when incorporated with saturated phospholipids.</p>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer potential of benzo[b]thiophene functionalized thiosemicarbazone ligands and their organoruthenium complexes.","authors":"Emine Öztürk, Elif Subaşı, Gizem Kurşunluoğlu, Betül Şen Yüksel, Hülya Ayar Kayalı","doi":"10.1007/s00775-024-02090-w","DOIUrl":"https://doi.org/10.1007/s00775-024-02090-w","url":null,"abstract":"<p><p>As novel promising anticancer candidates, the piano-stool type complexes of ruthenium, [RuCl(η⁶-p-cymene)(N,S-L_n)]PF₆, K₁-₄, were synthesized from the reaction of the substituted benzo[b]thiophene based thiosemicarbazone ligands (L_1-4) with [{RuCl(η⁶-p-cymene)}₂(μ-Cl)₂]. All complexes were fully characterized using elemental analysis, and spectroscopic methods such as FT-IR and ¹H NMR. The molecular masses of the complexes were proved by MALDI-TOF analysis. Single crystal X-ray diffraction study was employed in the structural elucidation of complex K₁ which shows a distorted octahedral geometry around the Ru(II) ion. Furthermore, spectroscopic methods revealed that in all complexes the ligands are coordinated to the metal center in neutral thione form via N, S donors. In this study, the effect of all ligands, complexes and commercial drugs with a different concentration on the viability of OVCAR-3, A2780 and OSE cells were compared. In this comparison, the cytotoxicity of ruthenium (II) complexes on two ovarian cancer cell lines (human A2780 and human OVCAR-3) was evaluated. For this purpose, the resazurin assay was performed. Based on our studies, complex K₂ showed the highest toxicity against OVCAR-3 and A2780 cells. The cytotoxic effect of K₂ was found to be higher than that of the commercial anticancer agents Oxalpin and Carbodex, 1.8-34.7-fold for OVCAR-3 cells and 1.9-11.8-fold for A2780 cells, respectively. These results provide insight into the potential of ruthenium (II) complexes as a cytotoxic agent for the treatment of ovarian cancer, particularly for primary tumors.</p>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iron-sulfur cluster redox chemistry and dimer dissociation in the outer mitochondrial membrane protein, mitoNEET.","authors":"Kanita A Chaudhry, Krishani K Rajanayake, Richard T Carroll, Dragan Isailovic, Max O Funk","doi":"10.1007/s00775-024-02093-7","DOIUrl":"https://doi.org/10.1007/s00775-024-02093-7","url":null,"abstract":"<p><p>The outer mitochondrial membrane protein known as mitoNEET was discovered when it was labeled by a photoaffinity derivative of the anti-diabetes medication, pioglitazone. The biological role for mitoNEET and its specific mechanism for achieving this remains an active subject for research. There is accumulating evidence suggesting that mitoNEET could be a component of mitochondrial FeS cofactor biogenesis. The protein was composed of an N-terminal membrane associated domain and a C-terminal domain oriented to the cytosol. The cytosolic domain was an iron-sulfur (2Fe-2S) metalloprotein with a rare 3Cys/1His coordination environment. It was previously reported that mitoNEET formed dimers that were remarkably sensitive to pH, likely a consequence of the protonation of the single His-iron ligand. The hypothesis pursued in the research reported here was that perhaps the dissociation of mitoNEET was also sensitive to the redox state of the iron sulfur cluster. To use native electrospray ionization mass spectrometry (ESI-MS) to monitor the reduction reaction ammonium dithionite was envisioned as the appropriate reagent to avoid sodium ion adduct formation from sodium dithionite. The preparation of ammonium dithionite was updated and the compound had the same properties as the sodium salt with redox dyes and the oxidized form of glutathione. The dissociation of mitoNEET treated with ammonium dithionite anaerobically was readily evident as ammonium dithionite was found to be compatible with redox chemistry evaluated by native ESI-MS.</p>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The nitrogenase mechanism: new roles for the dangler?","authors":"Rebeccah A Warmack, Douglas C Rees","doi":"10.1007/s00775-024-02085-7","DOIUrl":"https://doi.org/10.1007/s00775-024-02085-7","url":null,"abstract":"<p><p>Dangler sites protruding from a core metallocluster were introduced into the bioinorganic lexicon in 2000 by R.D. Britt and co-workers in an analysis of the tetramanganese oxygen-evolving cluster in photosystem II. In this perspective, we consider whether analogous dangler sites could participate in the mechanism of dinitrogen reduction by nitrogenase. Two possible roles for dynamic danglers in the active site FeMo cofactor are highlighted that might occur transiently during turnover. The first role for a dangler involves the S2B belt sulfur associated with displacement by carbon monoxide and other ligands, while the second dangler role could involve the entire cluster upon displacement of the His-  <math><mi>α</mi></math>  442 side chain to the molybdenum by a free carboxyl group of the homocitrate ligand. To assess whether waters might be able to interact with the cofactor, a survey of small ligands (water and alkali metal ions) contacting [4Fe4S] clusters in synthetic compounds and proteins was conducted. This survey reveals a preference for these sites to pack over the centers of 2Fe2S rhombs. Waters are excluded from the S2B site in the resting state of nitrogenase, suggesting it is unlikely that water molecules coordinate to the FeMo cofactor during catalysis. While alkali metal ions are found to generally influence the properties of catalysts for dinitrogen reduction, no convincing evidence was found that any of the waters near the FeMo cofactor could instead be sodium or potassium ions. Dangler sites, if they exist in the nitrogenase mechanism, are likely formed transiently by localized changes to the resting-state FeMo cofactor structure.</p>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}