Journal of Biological Inorganic Chemistry最新文献

{"title":"Initial characterization of an iron superoxide dismutase from Thermobifida fusca","authors":"Anne Grethe Hamre,&nbsp;Rim Al-Sadawi,&nbsp;Kirsti Merete Johannesen,&nbsp;Bastien Bisarro,&nbsp;Åsmund Røhr Kjendseth,&nbsp;Hanna-Kirsti S. Leiros,&nbsp;Morten Sørlie","doi":"10.1007/s00775-023-02019-9","DOIUrl":"10.1007/s00775-023-02019-9","url":null,"abstract":"<div><p>Superoxide dismutases (SODs) are enzymes that catalyze the dismutation of the superoxide radical anion into O₂ and H₂O₂ in a two-step reaction. They are ubiquitous to all forms of life and four different types of metal centers are detected, dividing this class of enzymes into Cu-/Zn-, Ni-, Mn-, and Fe-SODs. In this study, a superoxide dismutase from the thermophilic bacteria <i>Thermobifida fusca</i> (<i>Tf</i>SOD) was cloned and expressed before the recombinant enzyme was characterized. The enzyme was found to be active for superoxide dismutation measured by inhibition of cytochrome <i>c</i> oxidation and the inhibition of the autoxidation of pyrogallol. Its pH-optimum was determined to be 7.5, while it has a broad temperature optimum ranging from 20 to 90 °C. Combined with the <i>T</i>_m that was found to be 78.5 ± 0.5 °C at pH 8.0, <i>Tf</i>SOD can be defined as a thermostable enzyme. Moreover, the crystal structure of <i>Tf</i>SOD was determined and refined to 1.25 Å resolution. With electron paramagnetic resonance spectroscopy, it was confirmed that iron is the metal co-factor of <i>Tf</i>SOD. The cell potential (<i>E</i>_m) for the TfSOD-Fe³⁺/TfSOD-Fe²⁺ redox couple was determined to be 287 mV.</p><h3>Graphical abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 7","pages":"689 - 698"},"PeriodicalIF":3.0,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00775-023-02019-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41080279","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":"The formation of Fe3+-doxycycline complex is pH dependent: implications to doxycycline bioavailability","authors":"Jelena Korać Jačić,&nbsp;Milena Dimitrijević,&nbsp;Danica Bajuk-Bogdanović,&nbsp;Dalibor Stanković,&nbsp;Slađana Savić,&nbsp;Ivan Spasojević,&nbsp;Milica R. Milenković","doi":"10.1007/s00775-023-02018-w","DOIUrl":"10.1007/s00775-023-02018-w","url":null,"abstract":"<div><p>The interactions of drugs with iron are of interest in relation to the potential effects of iron-rich foods and iron supplements on sorption and bioavailability. Doxycycline (DOX), a member of the tetracycline class of broad-spectrum antibiotics, is frequently administered by oral route. In the digestive tract, DOX can be exposed to iron at different pH values (stomach pH 1.5–4, duodenum pH 5–6, distal jejunum and ileum pH 7–8). In relation to this, we analyzed the impact of pH on Fe³⁺-DOX complex formation. The optimal conditions for Fe³⁺-DOX complex formation are pH = 4 and [Fe³⁺]/[DOX] = 6 molar ratio. HESI-MS showed that Fe³⁺-DOX complex has 1:1 stoichiometry. Raman spectra of Fe³⁺-DOX complex indicate the presence of two Fe³⁺-binding sites in DOX structure: tricarbonylamide group of ring A and phenolic-diketone oxygens of BCD rings. The Fe³⁺-DOX complex formed at pH = 4 is less susceptible to oxidation than DOX at this pH. The increase of pH induces the decomposition of Fe³⁺-DOX complex without oxidative degradation of DOX. The pH dependence of Fe³⁺-DOX complex formation may promote unwanted effects of DOX, impeding the absorption that mainly takes place in duodenum. This could further result in higher concentrations in the digestive tract and to pronounced impact on gut microbiota.</p><h3>Graphical abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 7","pages":"679 - 687"},"PeriodicalIF":3.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41079734","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":"Fractionation of selenium isotopes during biofortification of Saccharomyces cerevisiae and the influence of metabolic labeling with 15N","authors":"Luis Fernando Mejia Diaz,&nbsp;Jakub Karasinski,&nbsp;Kazimierz Wrobel,&nbsp;Alma Rosa Corrales Escobosa,&nbsp;Eunice Yanez Barrientos,&nbsp;Ludwik Halicz,&nbsp;Ewa Bulska,&nbsp;Katarzyna Wrobel","doi":"10.1007/s00775-023-02016-y","DOIUrl":"10.1007/s00775-023-02016-y","url":null,"abstract":"<div><p>Isotope fractionation of metals/metalloids in biological systems is an emerging research area that demands the application of state-of-the-art analytical chemistry tools and provides data of relevance to life sciences. In this work, Se uptake and Se isotope fractionation were measured during the biofortification of baker’s yeast (<i>Saccharomyces cerevisiae</i>)—a product widely used in dietary Se supplementation and in cancer prevention. On the other hand, metabolic labeling with ¹⁵N is a valuable tool in mass spectrometry-based comparative proteomics. For Se-yeast, such labeling would facilitate the assessment of Se impact on yeast proteome; however, the question arises whether the presence of ¹⁵N in the microorganisms affects Se uptake and its isotope fractionation. To address the above-mentioned aspects, extracellularly reduced and cell-incorporated Se fractions were analyzed by hydride generation–multi-collector inductively coupled plasma–mass spectrometry (HG MC ICP–MS). It was found that extracellularly reduced Se was enriched in light isotopes; for cell-incorporated Se, the change was even more pronounced, which provides new evidence of mass fractionation during biological selenite reduction. In the presence of ¹⁵N, a weaker preference for light isotopes was observed in both, extracellular and cell-incorporated Se. Furthermore, a significant increase in Se uptake for ¹⁵N compared to ¹⁴N biomass was found, with good agreement between hydride generation microwave plasma–atomic emission spectrometry (HG MP–AES) and quadrupole ICP–MS results. Biological effects observed for heavy nitrogen suggest ¹⁵N-driven alteration at the proteome level, which facilitated Se access to cells with decreased preference for light isotopes.</p><h3>Graphical abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 7","pages":"655 - 667"},"PeriodicalIF":3.0,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41079722","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 mechanism of antiproliferative activity of the oxaliplatin pyrophosphate derivative involves its binding to nuclear DNA in cancer cells","authors":"Jitka Prachařová,&nbsp;Hana Kostrhunová,&nbsp;Alessandra Barbanente,&nbsp;Nicola Margiotta,&nbsp;Viktor Brabec","doi":"10.1007/s00775-023-02017-x","DOIUrl":"10.1007/s00775-023-02017-x","url":null,"abstract":"<div><p>(1R,2R-diaminocyclohexane)(dihydropyrophosphato) platinum(II), also abbreviated as RRD2, belongs to a class of potent antitumor platinum cytostatics called phosphaplatins. Curiously, several published studies have suggested significant mechanistic differences between phosphaplatins and conventional platinum antitumor drugs. Controversial findings have been published regarding the role of RRD2 binding to DNA in the mechanism of its antiproliferative activity in cancer cells. This prompted us to perform detailed studies to confirm or rule out the role of RRD2 binding to DNA in its antiproliferative effect in cancer cells. Here, we show that RRD2 exhibits excellent antiproliferative activity in various cancer cell lines, with IC₅₀ values in the low micromolar or submicromolar range. Moreover, the results of this study demonstrate that DNA lesions caused by RRD2 contribute to killing cancer cells treated with this phosphaplatin derivative. Additionally, our data indicate that RRD2 accumulates in cancer cells but to a lesser extent than cisplatin. On the other hand, the efficiency of cisplatin and RRD2, after they accumulate in cancer cells, in binding to nuclear DNA is similar. Our results also show that RRD2 in the medium, in which the cells were cultured before RRD2 accumulated inside the cells, remained intact. This result is consistent with the view that RRD2 is activated by releasing free pyrophosphate only in the environment of cancer cells, thereby allowing RRD2 to bind to nuclear DNA.</p><h3>Graphical abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 7","pages":"669 - 678"},"PeriodicalIF":3.0,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00775-023-02017-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41080301","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":"Sulfur-bridging the gap: investigating the electrochemistry of novel copper chelating agents for Alzheimer's disease applications","authors":"Emma Crnich,&nbsp;Erik Sanchez,&nbsp;Mallory A. Havens,&nbsp;Daniel S. Kissel","doi":"10.1007/s00775-023-02013-1","DOIUrl":"10.1007/s00775-023-02013-1","url":null,"abstract":"<div><p>There is currently an unmet demand for multi-functional precision treatments for Alzheimer's disease (AD) after several failed attempts at designing drugs based on the amyloid hypothesis. The focus of this work is to investigate sulfur-bridged quinoline ligands that could potentially be used in chelation therapies for a subpopulation of AD patients presenting with an overload of labile copper ions, which are known to catalyze the production of reactive oxygen species (ROS) and exacerbate other markers of AD progression. The ligands 1-(2′-thiopyridyl)isoquinoline (1TPIQ) and 2-(2′-thiopyridyl)quinoline (2TPQ) were synthesized and characterized before being electrochemically investigated in the presence of different oxidizing and reducing agents in solution with a physiological pH relevant to the brain. The electrochemical response of each compound with copper was studied by employing both hydrogen peroxide (H₂O₂) as an oxidizing agent and ascorbic acid (AA) as an antioxidant during analysis using cyclic voltammetry (CV). The cyclic voltammograms of each quinoline were compared with similar ligands that contained aromatic N-donor groups but no sulfur groups to provide relative electrochemical properties of each complex in solution. In a dose-dependent manner, it was observed that AA exerted dual-efficacy when combined with these chelating ligands: promoting synergistic metal binding while also scavenging harmful ROS, suggesting AA is an effective adjuvant therapeutic agent. Overall, this study shows how coordination by sulfur-bridged quinoline ligands can alter copper electrochemistry in the presence of AA to limit ROS production in solution.</p><h3>Graphical abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 7","pages":"643 - 653"},"PeriodicalIF":3.0,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41079967","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":"Nickel chloride complexes with substituted 4′-phenyl-2′,2′:6′,2″-terpyridine ligands: synthesis, characterization, anti-proliferation activity and biomolecule interactions","authors":"Benwei Wang,&nbsp;Dameng Sun,&nbsp;Sihan Wang,&nbsp;Min Chen,&nbsp;Hongming Liu,&nbsp;Yanling Zhou,&nbsp;Hailan Chen,&nbsp;Zhen Ma","doi":"10.1007/s00775-023-02011-3","DOIUrl":"10.1007/s00775-023-02011-3","url":null,"abstract":"<div><p>A series of Ni(II) sandwich-like coordinated compounds were synthesized by the reaction of nickel dichloride and ten 4′-(4-substituent phenyl)-2′,2′:6′,2″-terpyridine ligands, and their structures were confirmed by elemental analysis, FT-IR, ESI–MS, solid state ultraviolet spectroscopy and X-ray single crystal diffraction analysis. Three human cancer cell lines and a normal human cell line were used for anti-proliferation potential study: human lung cancer cell line (A549), human esophageal cancer cell line (Eca-109), human liver cancer cells (Bel-7402) and normal human liver cells (HL-7702). The results show that these nickel complexes possess good inhibitory effects on the cancer cells, outperforming the commonly used clinical chemotherapy drug cisplatin. Especially, complexes <b>3</b> (-methoxyl) and <b>7</b> (-fluoro) have strong inhibitory ability against Eca-109 cell line with IC₅₀ values of 0.223 μM and 0.335 μM, complexes <b>4</b> and <b>6</b> showed certain cell selectivity, and complex <b>6</b> can inhibit cancer cells and slightly poison normal cells when the concentration was controlled. The ability of these complexes binding to CT-DNA was studied by UV titration and CD spectroscopy, and CD spectroscopy was also used to study the secondary structural change of BSA under the action of the complexes. The binding of these complexes with DNA, DNA-Topo I and bovine serum protein has been simulated by molecular docking software, and the docking results and optimal binding conformation data showed that they interacted with DNA in the mode of embedded binding, which is consistent with the experimental results. These complexes are more inclined to move to the cleavage site when docking with DNA-Topo I, so as to play a role of enzyme cleavage, while BSA promotes the action of the complexes by binding to effective binding sites.</p><h3>Graphical abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 7","pages":"627 - 641"},"PeriodicalIF":3.0,"publicationDate":"2023-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41079915","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":"Peroxidase activity of rice (Oryza sativa) hemoglobin: distinct role of tyrosines 112 and 151","authors":"Valérie Derrien,&nbsp;Eric André,&nbsp;Sophie Bernad","doi":"10.1007/s00775-023-02014-0","DOIUrl":"10.1007/s00775-023-02014-0","url":null,"abstract":"<div><p>Five non-symbiotic hemoglobins (nsHb) have been identified in rice (<i>Oryza sativa</i>). Previous studies have shown that stress conditions can induce their overexpression, but the role of those globins is still unclear. To better understand the functions of nsHb, the reactivity of rice Hb1 toward hydrogen peroxide (H₂O₂) has been studied in vitro. Our results show that recombinant rice Hb1 dimerizes through dityrosine cross-links in the presence of H₂O₂. By site-directed mutagenesis, we suggest that tyrosine 112 located in the FG loop is involved in this dimerization. Interestingly, this residue is not conserved in the sequence of the five rice non-symbiotic hemoglobins. Stopped-flow spectrophotometric experiments have been performed to measure the catalytic constants of rice Hb and its variants using the oxidation of guaiacol. We have shown that Tyrosine112 is a residue that enhances the peroxidase activity of rice Hb1, since its replacement by an alananine leads to a decrease of guaiacol oxidation. In contrast, tyrosine 151, a conserved residue which is buried inside the heme pocket, reduces the protein reactivity. Indeed, the variant Tyr151Ala exhibits a higher peroxidase activity than the wild type. Interestingly, this residue affects the heme coordination and the replacement of the tyrosine by an alanine leads to the loss of the distal ligand. Therefore, even if the amino acid at position 151 does not participate to the formation of the dimer, this residue modulates the peroxidase activity and plays a role in the hexacoordinated state of the heme.</p><h3>Graphical abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 6","pages":"613 - 626"},"PeriodicalIF":3.0,"publicationDate":"2023-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00775-023-02014-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5118540","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":"Ga(III) pyridinecarboxylate complexes: potential analogues of the second generation of therapeutic Ga(III) complexes?","authors":"Michaela Rendošová,&nbsp;Róbert Gyepes,&nbsp;Simona Sovová,&nbsp;Danica Sabolová,&nbsp;Mária Vilková,&nbsp;Petra Olejníková,&nbsp;Martin Kello,&nbsp;Boris Lakatoš,&nbsp;Zuzana Vargová","doi":"10.1007/s00775-023-02012-2","DOIUrl":"10.1007/s00775-023-02012-2","url":null,"abstract":"<div><p>A series of novel Ga(III)—pyridine carboxylates ([Ga(Pic)₃]·H₂O (GaPic; HPic = picolinic acid), H₃O[Ga(Dpic)₂]·H₂O (GaDpic; H₂Dpic = dipicolinic acid), [Ga(Chel)(H₂O)(OH)]₂·4H₂O (GaChel; H₂Chel = chelidamic acid) and [Ga(Cldpic)(H₂O)(OH)]₂ (GaCldpic; H₂Cldpic = 4-chlorodipicolinic acid)) have been synthesized by simple one-step procedure. Vibrational spectroscopy (mid-IR), elemental analysis, thermogravimetric analysis and X-ray diffraction confirmed complexes molecular structure, inter and intramolecular interactions and their influence to spectral and thermal properties. Moreover, complex species speciation was described in Ga(III)-HPic and Ga(III)-H₂Dpic systems by potentiometry and ¹H NMR spectroscopy and mononuclear complex species were determined; [Ga(Pic)₂]⁺ (log<i>β</i>_<i>021</i> = 16.23(6)), [Ga(Pic)₃] (log<i>β</i>_<i>031</i> = 20.86(2)), [Ga(Dpic)₂]⁻ (log<i>β</i>_<i>021</i> = 15.42(9)) and [Ga(Dpic)₂(OH)]²⁻ (log<i>β</i>_<i>-121</i> = 11.08(4)). To confirm the complexes stability in 1% DMSO (primary solvent for biological testing), timescale ¹H NMR spectra were measured (immediately after dissolution up to 96 h). Antimicrobial activity evaluated by IC₅₀ (0.05 mM) is significant for GaDpic and GaCldpic against difficult to treat and multi-resistant <i>P. aeruginosa</i>. On the other hand, the GaPic complex is most effective against Jurkat, MDA-MB-231 and A2058 cancer cell lines and significantly also decreases the HepG2 cancer cells viability at 75 and 100 μM concentrations in a relatively short time (up to 48 h). In addition, fluorescence measurements have been used to elucidate bovine serum albumin binding activity between ligands, Ga(III) complexes and bovine serum albumin.</p><h3>Graphical abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 6","pages":"591 - 611"},"PeriodicalIF":3.0,"publicationDate":"2023-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00775-023-02012-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5042763","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":"The adducts of cyano- and aquacobalamin with hypochlorite","authors":"Maria Lehene,&nbsp;Adrian M. V. Brânzanic,&nbsp;Radu Silaghi-Dumitrescu","doi":"10.1007/s00775-023-02015-z","DOIUrl":"10.1007/s00775-023-02015-z","url":null,"abstract":"<div><p>Hypochlorite is known to oxidatively degrade the corrin ring of cobalamin. Here, transient reaction intermediates are described in the reaction of aqua as well as of cyano-cobalamin with hypochlorite, using stopped-flow UV–vis kinetics. For aqua-cobalamin, the intermediate is assigned as arising from substitution of the aqua ligand with hypochlorite. For cyano-cobalamin, the intermediate is proposed to arise from substitution of the benzimidazole ligand trans to the cyanide. In both cases, the intermediates would feature a new Co(III)-OCl⁻bond—which is also supported by density functional theory (DFT) calculations.</p><h3>Graphical abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 6","pages":"583 - 589"},"PeriodicalIF":3.0,"publicationDate":"2023-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00775-023-02015-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5011645","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":"meso-Bromination of cyano- and aquacobalamins facilitates their processing into Co(II)-species by glutathione","authors":"Ilia A. Dereven’kov,&nbsp;Vladimir S. Osokin,&nbsp;Ilya A. Khodov,&nbsp;Valentina V. Sobornova,&nbsp;Nikita A. Ershov,&nbsp;Sergei V. Makarov","doi":"10.1007/s00775-023-02009-x","DOIUrl":"10.1007/s00775-023-02009-x","url":null,"abstract":"<div><p>Cyanocobalamin (CNCbl), a medicinal form of vitamin B₁₂, is resistant to glutathione (GSH), and undergoes intracellular processing via reductive decyanation producing the Co(II)-form of Cbl (Cbl(II)) mediated by the CblC-protein. Alteration of the CblC-protein structure might inhibit CNCbl processing. Here, we showed that introducing a bromine atom to the C10-position of the CNCbl corrin ring facilitates its reaction with GSH leading to the formation of Cbl(II) and cyanide dissociation. In a neutral medium, the reaction between C10-Br-CNCbl and GSH proceeds via the complexation of the reactants further leading to dimethylbenzimidazole (DMBI) substitution and electron transfer from GSH to the Co(III)-ion. The reaction is accelerated upon the GSH thiol group deprotonation. The key factors explaining the higher reactivity of C10-Br-CNCbl compared with unmodified CNCbl towards GSH are increasing the electrode potential of CNCbl two-electron reduction upon meso-bromination and the substantial labilization of DMBI, which was shown by comparing their reactions with cyanide and the p<i>K</i>_a values of DMBI protonation (p<i>K</i>_{a base-off}). Aquacobalamin (H₂OCbl) brominated at the C10-position of the corrin reacts with GSH to give Cbl(II) via GSH complexation and subsequent reaction of this complex with a second GSH molecule, whereas unmodified H₂OCbl generates glutathionyl-Cbl, which is resistant to further reduction by GSH.</p><h3>Graphical abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 6","pages":"571 - 581"},"PeriodicalIF":3.0,"publicationDate":"2023-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4865036","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}