Journal of Biological Inorganic Chemistry最新文献

{"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}

{"title":"Globin ferryl species: what is the nature of the protonation event at pH < 5?","authors":"Cezara Zagrean-Tuza, Lavinia Padurean, Maria Lehene, Adrian M V Branzanic, Radu Silaghi-Dumitrescu","doi":"10.1007/s00775-024-02089-3","DOIUrl":"https://doi.org/10.1007/s00775-024-02089-3","url":null,"abstract":"<p><p>The ferryl state in globins has previously been reported to undergo a protonation event below pH 5, as assessed using pH jump experiments with stopped-flow UV-Vis spectroscopy. This protonation entails hypsochromic shifts in the α and β bands (~ 20 to 40 nm) and an ~ 10 nm reduction in the energy difference between these two bands. We now report that in Mb this event is also characterized by a hypsochromic shift in the Soret band (~ 5 nm). No similar shifts in Soret, α, and β bands are seen upon the denaturation of ferryl Mb with guanidine-suggesting that the spectroscopic changes in ferryl Mb at pH < 5 are not caused by changes in the solvent exposure or in hydrogen bonding around the ferryl unit. Under the same denaturing conditions (pH jump below pH 5, and/or guanidine), ferric-aqua and ferrous-oxy Mb show no spectral changes of the order seen in the ferryl pH jump experiments. Together, these observations suggest that the protonation event is localized on the iron-bound oxygen atom, as opposed to somewhere on a hydrogen-bonding partner. Time-dependent density functional theory (TD-DFT) calculations were not able to systematically predict the UV-Vis spectra of the heme to the level of detail needed to interpret the experimental findings in this study.</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":"142851753","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":"Shift of cell-death mechanisms in primary human neutrophils with a ruthenium photosensitizer.","authors":"Nicolás Montesdeoca, Jennifer M Mohr, Sebastian Kruss, Johannes Karges","doi":"10.1007/s00775-024-02088-4","DOIUrl":"https://doi.org/10.1007/s00775-024-02088-4","url":null,"abstract":"<p><p>Primary human neutrophils are the most abundant human white blood cells and are central for innate immunity. They act as early responders at inflammation sites, guided by chemotactic gradients to find infection or inflammation sites. Neutrophils can undergo both apoptosis as well as NETosis. NETosis is a form of neutrophil cell death that releases chromatin-based extracellular traps (NETs) to capture and neutralize pathogens. Understanding or controlling the balance between these cell-death mechanisms is crucial. In this study, the chemical synthesis and biologic assessment of a ruthenium complex as a light-activated photosensitizer that creates reactive oxygen species (ROS) in primary human neutrophils is reported. The ruthenium complex remains non-toxic in the dark. However, upon exposure to blue light at 450 nm, it exhibits potent cytotoxic effects in both cancerous and non-cancerous cell lines. Interestingly, the metal complex shifts the cell-death mechanism of primary human neutrophils from NETosis to apoptosis. Cells irradiated directly by the light source immediately undergo apoptosis, whereas those further away from the light source perform NETosis at a slower rate. This indicates that high ROS levels trigger apoptosis and lower ROS levels NETosis. The ability to control the type of cell death undergone in primary human neutrophils could have implications in managing acute and chronic infectious diseases.</p>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823895","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":"NifEN: a versatile player in nitrogenase assembly, catalysis and evolution.","authors":"Yilin Hu, Markus W Ribbe","doi":"10.1007/s00775-024-02086-6","DOIUrl":"https://doi.org/10.1007/s00775-024-02086-6","url":null,"abstract":"<p><p>The Mo-nitrogenase catalyzes the reduction of N₂ to NH₃ at the cofactor of its catalytic NifDK component. NifEN shares considerable homology with NifDK in primary sequence, tertiary structure and associated metallocenters. Better known for its biosynthetic function to convert an all-iron precursor (L-cluster; [Fe₈S₉C]) to a mature cofactor (M-cluster; [(R-homocitrate) MoFe₇S₉C]), NifEN also mimics NifDK in catalyzing substrate reduction at ambient conditions. The recently discovered ability of NifEN to reduce N₂ to NH₃ is particularly interesting, as it points to NifEN as a plausible, prototype ancient nitrogenase during evolution. Moreover, the dual function of NifEN in assembly and catalysis makes it a great template to reconstruct the functional variants or equivalents of NifDK, which could facilitate the mechanistic investigation and heterologous synthesis of nitrogenase. This perspective provides an overview of our recent studies of NifEN, with a focus on the implications of its functional versatility for nitrogenase assembly, catalysis and evolution.</p>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811803","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":"Insights into periplasmic nitrate reductase function under single turnover","authors":"Jennifer McGarry,&nbsp;Breeanna Mintmier,&nbsp;Mikayla C. Metzger,&nbsp;Nitai C. Giri,&nbsp;Nicholas Britt,&nbsp;Partha Basu,&nbsp;Jarett Wilcoxen","doi":"10.1007/s00775-024-02087-5","DOIUrl":"10.1007/s00775-024-02087-5","url":null,"abstract":"<div><p>Nitrate reductases play pivotal roles in nitrogen metabolism by leveraging the molybdopterin cofactor to facilitate the reduction of nitrate to nitrite. Periplasmic nitrate reductases (NapA) utilize nitrate as a terminal electron acceptor when oxygen is limiting, helping to drive anaerobic metabolism in bacteria. Despite extensive research into NapA homologs, open questions about the mechanism remain especially at the molecular level. More broadly, little is understood of how the molybdopterin cofactor is tuned for catalysis in these enzymes enabling broad substrate scope and reactivity observed in molybdenum-containing enzymes. Here, we have prepared NapA from <i>Campylobacter jejuni</i> under single turnover conditions to generate a singly reduced enzyme that can be further examined by electron paramagnetic resonance (EPR) spectroscopy. Our results provide new context into the known spectra and related structures of NapA and related enzymes. These insights open new avenues for understanding nitrate reductase mechanisms, molybdenum coordination dynamics, and the role of pyranopterin ligands in catalysis.</p></div>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":"29 7-8","pages":"811 - 819"},"PeriodicalIF":2.7,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778874","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":"In situ detection of ferric reductase activity in the intestinal lumen of an insect","authors":"Anna Karen Hernández-Gallardo,&nbsp;Trinidad Arcos-López,&nbsp;Jahir Marceliano Bahena-Lopez,&nbsp;Carlos Tejeda-Guzmán,&nbsp;Salvador Gallardo-Hernández,&nbsp;Samuel M. Webb,&nbsp;Thomas Kroll,&nbsp;Pier Lorenzo Solari,&nbsp;Carolina Sánchez-López,&nbsp;Christophe Den Auwer,&nbsp;Liliana Quintanar,&nbsp;Fanis Missirlis","doi":"10.1007/s00775-024-02080-y","DOIUrl":"10.1007/s00775-024-02080-y","url":null,"abstract":"<div><p>The rise of atmospheric oxygen as a result of photosynthesis in cyanobacteria and chloroplasts has transformed most environmental iron into the ferric state. In contrast, cells within organisms maintain a reducing internal milieu and utilize predominantly ferrous iron. Ferric reductases are enzymes that transfer electrons to ferric ions, either extracellularly or within endocytic vesicles, enabling cellular ferrous iron uptake through Divalent Metal Transporter 1. In mammals, duodenal cytochrome b is a ferric reductase of the intestinal epithelium, but how insects reduce and absorb dietary iron remains unknown. Here we provide indirect evidence of extracellular ferric reductase activity in a small subset of <i>Drosophila melanogaster</i> intestinal epithelial cells, positioned at the neck of the midgut’s anterior region. Dietary-supplemented bathophenanthroline sulphate (BPS) captures locally generated ferrous iron and precipitates into pink granules, whose chemical identity was probed combining in situ X-ray absorption near edge structure and electron paramagnetic resonance spectroscopies. An increased presence of manganese ions upon BPS feeding was also found. Control animals were fed with ferric ammonium citrate, which is accumulated into ferritin iron in distinct intestinal subregions suggesting iron trafficking between different cells inside the animal. Spectroscopic signals from the biological samples were compared to purified <i>Drosophila</i> and horse spleen ferritin and to chemically synthesized BPS-iron and BPS-manganese complexes. The results corroborated the presence of BPS-iron in a newly identified ferric iron reductase region of the intestine, which we propose constitutes the major site of iron absorption in this organism.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":"29 7-8","pages":"773 - 784"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00775-024-02080-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective binding and removal of copper from biological fluids—why are PSP ligands so efficient?","authors":"Peter Faller","doi":"10.1007/s00775-024-02082-w","DOIUrl":"10.1007/s00775-024-02082-w","url":null,"abstract":"<div><p>The following comment tries to answer why the reported removal of copper from buffer, cell culture medium, and cell extract by a supported chelator called phenPS is so selective and efficient. It is further argued that the family of PSP (phosphine sulfide-stabilized phosphines) chelators, due to their unique properties, have various potential future application in biology and medicine such as chelation therapy, copper-sensors, or tools to understand copper metabolism.</p></div>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":"29 7-8","pages":"639 - 640"},"PeriodicalIF":2.7,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754504","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":"Vanadium complexes as potential metal-based antimicrobial drugs","authors":"Meena Kumari,&nbsp;Maridula Thakur,&nbsp;Sonika Sharma,&nbsp;Mala Sharma,&nbsp;Vineet Kumar Choudhary,&nbsp;Reena Sharma,&nbsp;Shubham Sharma,&nbsp;Shalima Kumari,&nbsp;Sachin Kumar","doi":"10.1007/s00775-024-02084-8","DOIUrl":"10.1007/s00775-024-02084-8","url":null,"abstract":"<div><p>Radical increase of antibiotic resistance among microbes has become a serious problem for clinics all over the world that has led to the need for search of novel types of antimicrobial drugs. Each year, researchers synthesize a multitude of compounds in pursuit of identifying potential chemotherapeutic agents through diverse methodological evaluations. Among the vast array of biologically significant compounds, coordination compounds exhibit a broad range of activities within biological systems. Chelation, in particular, induces significant alterations in the biological properties of ligands and the metal component, contributing to their efficacy. Chelation increases the lipophilicity of metal complexes as a result of which they are easily absorbed by the microorganisms, thus leading to their easy passage across cell membrane. The research and development in the field of metallodrugs can be advantageous to overcome the problem encountered in antibiotic resistance. The multifaceted involvement of vanadium relative to other biometals within biological systems, coupled with its comparatively lower toxicity, underscores its utility in the advancement of novel metal-based therapeutic agents. This review aims to delineate the biological significance of V(V/IV/III) complexes as antimicrobial agents. The amassed data indicate a correlation between the potency of vanadium complexes as antimicrobial agents and the oxidation state of the metal, with III being the least toxic and V representing the most toxic oxidation state of vanadium.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"29 7-8","pages":"685 - 706"},"PeriodicalIF":2.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724589","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":"Evaluation of Au(III) complexes as Plasmodium falciparum aquaglyceroporin (PfAQP) inhibitors by in silico and in vitro methods","authors":"Federico Balgera,&nbsp;Muyideen Kolapo Tijani,&nbsp;Johan Wennerberg,&nbsp;Kristina E. M. Persson,&nbsp;Ebbe Nordlander,&nbsp;Ricardo J. Ferreira","doi":"10.1007/s00775-024-02081-x","DOIUrl":"10.1007/s00775-024-02081-x","url":null,"abstract":"<div><p>The onset of resistance to artemisinin for malaria treatment has stimulated the quest for novel antimalarial drugs. Herein, the gold(III) coordination complexes Aubipy [Au(bipy)Cl]⁺ (bipy = 2,2′-bipyridine), Auphen [Au(phen)Cl]⁺ (phen = phenanthroline), Auterpy [Au(terpy)Cl]²⁺ (terpy = 2,2′;6′,2″-terpyridine), and corresponding hydrolyzed species, have been investigated as inhibitors of the <i>Plasmodium falciparum</i> aquaglyceroporin (<i>Pf</i>AQP) protein by computational methods. Through an <i>in-silico</i> approach using an Umbrella Sampling protocol to sample how Aubipy, Auphen, and Auterpy permeate through the <i>Pf</i>AQP, their permeability coefficients were estimated using the Inhomogeneous Solubility Diffusion (ISD) model with promising results. The efficacy of the gold complexes was then probed by an in vitro assay testing the growth inhibition in chloroquine sensitive and resistant <i>P. falciparum</i> strains. In accordance with the computational data, Auterpy achieved the highest efficiency with an IC₅₀ in the nanomolar range (590 nM) on resistant strain cultures, additionally revealing a good selectivity as compared to its activity against the human aquaglyceroporin 3.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"29 7-8","pages":"821 - 836"},"PeriodicalIF":2.7,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695115","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":"Ascorbate: a forgotten component in the cytotoxicity of Cu(II) ATCUN peptide complexes","authors":"Julian Heinrich,&nbsp;Elisa Siddiqui,&nbsp;Henrike Eckstein,&nbsp;Michael Naumann,&nbsp;Nora Kulak","doi":"10.1007/s00775-024-02083-9","DOIUrl":"10.1007/s00775-024-02083-9","url":null,"abstract":"<div><p>In 1983, Linus Pauling and colleagues reported about enhanced antitumor activity of the Cu(II) complex of the simplest ATCUN (amino terminal Cu(II) and Ni(II)-binding motif) peptide (NH₂-Gly-Gly-His-COOH, GGH) in the presence of ascorbate as an additive. In the following 4 decades, structural modifications of this complex were implemented, however, anticancer activity could not be significantly increased. This has led to neglecting the ATCUN motif and its Cu(II) complexes as potential chemotherapeutic agents. Furthermore, the addition of ascorbate with its positive effect on the anticancer activity has fallen into oblivion. In this work, we compared Cu(II) GGH with Cu(II) ATCUN peptides bearing β-Ala instead of Gly at the 2nd position of the peptide sequence regarding their in vitro complex stability and cytotoxicity (MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and annexin V-FITC (fluorescein isothiocyanate) apoptosis assay) towards three cancer cell lines (AGS, HeLa and NCI-N87). Such an exchange of amino acids led to an up to three-fold higher cytotoxic effect in the presence of ascorbate. We thus achieved a significant increase in the otherwise moderate cytotoxicity of Cu(II) ATCUN-like complexes. Lipophilicity assays (<i>n</i>-octanol/water coefficient, log <i>P</i> values) of the studied complexes were used to evaluate differences in the antiproliferative activity.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"29 7-8","pages":"801 - 809"},"PeriodicalIF":2.7,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00775-024-02083-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}