JBIC Journal of Biological Inorganic Chemistry最新文献

{"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}

{"title":"Interactions of arene ruthenium(II) complexes [η6-(C6H6)Ru(pprip)Cl]+ and [η6-(C6H6)Ru(H2iiP)Cl]+ with RNA triplex poly(U)•poly(A)*poly(U)","authors":"Feng Yuan,&nbsp;Xiaohua Liu,&nbsp;Juan Li,&nbsp;Lifeng Tan","doi":"10.1007/s00775-023-02008-y","DOIUrl":"10.1007/s00775-023-02008-y","url":null,"abstract":"<div><p>Two arene ruthenium(II) complexes [<i>η</i>⁶-(C₆H₆)Ru(pprip)Cl]PF₆ (Ru<b>1</b>; pprip = 2-(3-phenyl-1H-pyrazol-4-yl)-imidazolo[4,5-<i>f</i>][1,10]phenanthroline) and [<i>η</i>⁶-(C₆H₆)Ru(H₂iiP)Cl]PF₆ (Ru<b>2</b>; H₂iiP = 2-(indole-3-yl)-imidazolo[4,5-<i>f</i>][1,10]phenanthroline) have been synthesized and characterized in this work. Binding properties of Ru<b>1</b> and Ru<b>2</b> with the triplex RNA poly(U)•poly(A)*poly(U) were investigated by spectrophotometry and spectrofluorometry as well as viscosimetry. Analysis of spectroscopic titrations and viscosity measurements show that the two complexes bind with the triplex through intercalation, while the binding affinity for Ru<b>2</b> toward the triplex is stronger than that for Ru<b>1</b>. Melting experiments indicate that the stabilizing effects of Ru<b>1</b> and Ru<b>2</b> toward the triplex differ from each other. Under the conditions used herein, Ru<b>1</b> only stabilizes the Hoogsteen base-paired strand (third strand) without affecting stabilization of the Watson–Crick base-paired strand (the template duplex) of the triplex, while Ru<b>2</b> stabilizes both the template duplex and the third strand. Although the two complexes prefer to stabilizing the third strand rather than the template duplex, the third-strand stabilization effect of Ru<b>2</b> is stronger than that of Ru<b>1</b>. The obtained results of this work reveal that the planarity of the intercalative ligands plays an important role in the triplex stabilization by arene Ru(II) complexes.</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":"559 - 570"},"PeriodicalIF":3.0,"publicationDate":"2023-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4824316","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":"Ferrocene-based nitroheterocyclic sulfonylhydrazones: design, synthesis, characterization and trypanocidal properties","authors":"Miguel Gallardo,&nbsp;Rodrigo Arancibia,&nbsp;Claudio Jiménez,&nbsp;Shane Wilkinson,&nbsp;Patricia M. Toro,&nbsp;Pascal Roussel,&nbsp;Natacha Henry","doi":"10.1007/s00775-023-02010-4","DOIUrl":"10.1007/s00775-023-02010-4","url":null,"abstract":"<div><p>A series of new ferrocenyl nitroheterocyclic sulfonylhydrazones (<b>1a</b>–<b>4a</b> and <b>1b</b>–<b>2b</b>) were prepared by the reaction between formyl (R = H) or acetyl (R = CH₃) nitroheterocyclic precursors [4/5-NO₂(C₅H₂XCOR), where X = O, S)] and ferrocenyl tosyl hydrazine [(η⁵-C₅H₅)Fe(η⁵-C₅H₄SO₂-NH-NH₂)]. All compounds were characterized by conventional spectroscopic techniques. In the solid state, the molecular structures of compounds <b>1a</b>, <b>2b</b>, and <b>3a</b> were determined by single-crystal X–ray diffraction. The compounds showed an <i>E</i>-configuration around the C=N moiety. Evaluation of trypanocidal activity, measured in vitro against the <i>Trypanosoma cruzi</i> and <i>Trypanosoma brucei</i> strains, indicated that all organometallic tosyl hydrazones displayed activity against both parasite species with a higher level of potency toward <i>T. brucei</i> than <i>T. cruzi</i>. Moreover, the biological evaluation showed that the 5-nitroheterocyclic derivatives were more efficient trypanocidal agents than their 4-nitroheterocyclic counterparts.</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":"549 - 558"},"PeriodicalIF":3.0,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4722096","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":"Control of nutrient metal availability during host-microbe interactions: beyond nutritional immunity","authors":"Karrera Y. Djoko","doi":"10.1007/s00775-023-02007-z","DOIUrl":"10.1007/s00775-023-02007-z","url":null,"abstract":"<div><p>The control of nutrient availability is an essential ecological function of the host organism in host-microbe systems. Although often overshadowed by macronutrients such as carbohydrates, micronutrient metals are known as key drivers of host-microbe interactions. The ways in which host organisms control nutrient metal availability are dictated by principles in bioinorganic chemistry. Here I ponder about the actions of metal-binding molecules from the host organism in controlling nutrient metal availability to the host microbiota. I hope that these musings will encourage new explorations into the fundamental roles of metals in the ecology of diverse host-microbe systems.</p></div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 5","pages":"451 - 456"},"PeriodicalIF":3.0,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00775-023-02007-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4724285","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":"Ferrozoles: Ferrocenyl derivatives of letrozole with dual effects as potent aromatase inhibitors and cytostatic agents","authors":"Borja Diaz de Greñu,&nbsp;Diego M. Fernández-Aroca,&nbsp;Juan A. Organero,&nbsp;Gema Durá,&nbsp;Felix Angel Jalón,&nbsp;Ricardo Sánchez-Prieto,&nbsp;M. José Ruiz-Hidalgo,&nbsp;Ana María Rodríguez,&nbsp;Lucia Santos,&nbsp;José L. Albasanz,&nbsp;Blanca R. Manzano","doi":"10.1007/s00775-023-02006-0","DOIUrl":"10.1007/s00775-023-02006-0","url":null,"abstract":"<div><p>In the treatment of hormone-dependent cancers, aromatase inhibitors (AI) are receiving increased attention due to some undesirable effects such as the risk of endometrial cancer and thromboembolism of SERMs (selective estrogen receptor modulators). Letrozole is the most active AI with 99% aromatase inhibition. Unfortunately, this compound also exhibits some adverse effects such as hot flashes and fibromyalgias. Therefore, there is an urgent need to explore new types of AIs that retain the same—or even increased—antitumor ability. Inspired by the letrozole structure, a set of new derivatives has been synthesized that include a ferrocenyl moiety and different heterocycles. The derivative that contains a benzimidazole ring, namely compound <b>6</b>, exhibits a higher aromatase inhibitory activity than letrozole and it also shows potent cytostatic behavior when compared to other well-established aromatase inhibitors, as demonstrated by dose–response, cell cycle, apoptosis and time course experiments. Furthermore, <b>6</b> promotes the inhibition of cell growth in both an aromatase-dependent and -independent fashion, as indicated by the study of A549 and MCF7 cell lines. Molecular docking and molecular dynamics calculations on the interaction of <b>6</b> or letrozole with the aromatase binding site revealed that the ferrocene moiety increases the van der Waals and hydrophobic interactions, thus resulting in an increase in binding affinity. Furthermore, the iron atom of the ferrocene fragment can form a metal-acceptor interaction with a propionate fragment, and this results in a stronger coupling with the heme group—a possibility that is consistent with the strong aromatase inhibition of <b>6</b>.</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":"531 - 547"},"PeriodicalIF":3.0,"publicationDate":"2023-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4686536","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":"New platinum (II) complexes based on schiff bases: synthesis, specification, X-ray structure, ADMET, DFT, molecular docking, and anticancer activity against breast cancer","authors":"Mahboube Eslami Moghadam,&nbsp;Maryam Hasanzadeh Esfahani,&nbsp;Mahdi Behzad,&nbsp;Samaneh Zolghadri,&nbsp;Nadali Ramezani,&nbsp;Yasaman Azadi","doi":"10.1007/s00775-023-02005-1","DOIUrl":"10.1007/s00775-023-02005-1","url":null,"abstract":"<div><p>Acylpyrazolone-based Schiff base ligands (HL^<i>n</i>) and their corresponding Pt(II) complexes with the general formula [Pt(L^<i>n</i>)(Cl)] (<i>n</i>?=?1–3)?were synthesized and characterized by different spectroscopic techniques including ¹H-NMR, ¹⁹⁵Pt-NMR, LC-Mass, FT–IR, and UV–Vis spectroscopy, as well as elemental analysis. The crystal structure of one of the Schiff base ligands was also obtained. Based on the ADMET comparative results and the bioavailability radar charts, the complexes are completely drug-like. The Schiff base complexes with a structural difference of one methyl group in ligand were used as anticancer agents against human breast cancer cell lines SKBR3 and MDA-MB-231. The IC₅₀ values after treatment by [Pt(L¹)Cl] and [Pt(L²)Cl] were obtained more than cisplatin and less than carboplatin on cancer cells MDA-MB-231 and SKBR3, while the IC₅₀ value of [Pt(L³)Cl] was more than both other complexes and clinical Pt drugs. Molecular docking data showed that the groove binding is the main interaction with DNA double strands with a minor contribution from electrostatic interactions. To investigate the structure–activity relationship, DFT computational was done. All quantum chemical parameters display the drug approaching biomacromolecule and more biological activity of [Pt(L¹)Cl]?&gt;?[Pt(L²)Cl]?&gt;?[Pt(L³)Cl]. So, three Schiff base platinum complexes can be suitable candidates as anticancer drugs.</p><h3>Graphical abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div><div><p>Schiff-base ligands (HLn) and their Pt(II) complexes ([Pt(Ln)(Cl)], n=1-3) were obtained. To investigate their biological property and main interactions with DNA, ADMET, and cytotoxicity against MDA-MB-231 and SKBR3, DFT, and Molecular docking were done.</p></div></div></div></figure>\u0000 </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 5","pages":"519 - 529"},"PeriodicalIF":3.0,"publicationDate":"2023-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00775-023-02005-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4611635","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":"Binding and stabilizating effect of RNA triplex poly(U)⋅poly(A)*poly(U) by enantiomers of ruthenium(II) polypyridyl complex [Ru(bpy)2(dppx)]2+","authors":"Bingxin Wen,&nbsp;Xiaohua Liu,&nbsp;Lifeng Tan","doi":"10.1007/s00775-023-02004-2","DOIUrl":"10.1007/s00775-023-02004-2","url":null,"abstract":"<div><p>Two chiral ruthenium(II) polypyridyl complexes, Λ-[Ru(bpy)₂(dppx)]²⁺ (bpy?=?2,2′-bipyridine, dppx?=?7,8-dimethyldipyridophenazine; Λ-<b>1</b>) and Δ-[Ru(bpy)₂(dppx)]²⁺ (Δ-<b>1</b>) have been synthesized and characterized in this work. Interactions of Λ-<b>1</b> and Δ-<b>1</b> with the RNA triplex poly(U)?poly(A)*poly(U) have been investigated by various biophysical techniques. Spectrophotometric titrations and viscosity measurements suggested that enantiomers Λ-<b>1</b> and Δ-<b>1</b> bind with the triplex through intercalation, while the binding strengths of the two enantiomers toward the triplex differed only slightly from each other. Fluorescence titrations showed that although enantiomers Λ-<b>1</b> and Δ-<b>1</b> exhibited molecular “light switch” effects toward the triplex, the effect of Δ-<b>1</b> was more marked. Furthermore, Furthermore, thermal denaturation showed that the two enantiomers have significantly different stabilizing effects on the triplex. The obtained results indicate that the racemic complex [Ru(bpy)₂(dppx)]²⁺ is similar to a non-specific metallointercalator for the triplex investigated in this study, and chiralities of Ru(II) polypyridine complexes have an important influence on the binding and stabilizing effects of enantiomers toward the triplex.</p><h3>Graphical abstract</h3><p>Two chiral ruthenium(II) polypyridyl complexes, Λ-[Ru(bpy)₂(dppx)]²⁺ (bpy?=?2,2′-bipyridine, dppx?=?7,8-dimethyldipyridophenazine; Λ-<b>1</b>) and Δ-[Ru(bpy)₂(dppx)]²⁺ (Δ-<b>1</b>) have been synthesized and characterized in this work. Interactions of Λ-<b>1</b> and Δ-<b>1</b> with the RNA triplex poly(U)?poly(A)*poly(U) have been investigated by various biophysical techniques. The obtained results indicate that the racemic complex [Ru(bpy)₂(dppx)]²⁺ is similar as a non-specific metallointercalator for the triplex investigated in this study, and chiralities of Ru(II) polypyridine complexes have an important influence on the binding and stabilizing effects of enantiomers toward the triplex</p>\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 5","pages":"509 - 517"},"PeriodicalIF":3.0,"publicationDate":"2023-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00775-023-02004-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4614388","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":"Development and application of metallo-phthalocyanines as potent G-quadruplex DNA binders and photosensitizers","authors":"Ariadna Gil-Martínez,&nbsp;Adrián Hernández,&nbsp;Cristina Galiana-Roselló,&nbsp;Sònia López-Molina,&nbsp;Javier Ortiz,&nbsp;Ángela Sastre-Santos,&nbsp;Enrique García-España,&nbsp;Jorge González-García","doi":"10.1007/s00775-023-02003-3","DOIUrl":"10.1007/s00775-023-02003-3","url":null,"abstract":"<div><p>Metallo-phthalocyanines (<b>MPc</b>) are common photosensitizers with ideal photophysical and photochemical properties. Also, these molecules have shown to interact with non-canonical nucleic acid structures, such as G-quadruplexes, and modulate oncogenic expression in cancer cells. Herein, we report the synthesis and characterisation of two metallo-phthalocyanines containing either zinc (<b>ZnPc</b>) or nickel (<b>NiPc</b>) in the central aromatic core and four alkyl ammonium lateral chains. The interaction of both molecules with G-quadruplex DNA was assessed by UV–Vis, fluorescence and FRET melting experiments. Both molecules bind strongly to G-quadruplexes and stabilise these structures, being <b>NiPc</b> the most notable G-quadruplex stabiliser. In addition, the photosensitizing ability of both metal complexes was explored by the evaluation of the singlet oxygen generation and their photoactivation in cells. Only <b>ZnPc</b> showed a high singlet oxygen generation either by direct observation or by indirect evaluation using a DPBF dye. The cellular evaluation showed mainly cytoplasmic localization of <b>ZnPc</b> and a decrease of the IC₅₀ values of the cell viability of <b>ZnPc</b> upon light activation of two orders of magnitude.</p><h3>Graphical abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div><div><p>Two metallo-phthalocyanines containing zinc and nickel within the aromatic core have been investigated as G-quadruplex stabilizers and photosensitizers.<b> NiPc</b> shows a high G4 binding but negligible photosensitizing ability while<b> ZnPc</b> exhibits a moderate binding to G-quadruplex together with a high potency to generate singlet oxygen and photocytotoxicity. The interaction with G4s and capacity to be photosensitized is associated with the geometry adopted by the central metal core of the phthalocyanine scaffold.</p></div></div></div></figure>\u0000 </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 5","pages":"495 - 507"},"PeriodicalIF":3.0,"publicationDate":"2023-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00775-023-02003-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4574739","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":"Disruption of zinc (II) binding and dimeric protein structure of the XIAP-RING domain by copper (I) ions","authors":"Kathryn E. Splan,&nbsp;Sylvia R. Choi,&nbsp;Ruth E. Claycomb,&nbsp;Isaiah K. Eckart-Frank,&nbsp;Shreya Nagdev,&nbsp;Madeline E. Rodemeier","doi":"10.1007/s00775-023-02002-4","DOIUrl":"10.1007/s00775-023-02002-4","url":null,"abstract":"<div><p>Modulation of metalloprotein structure and function via metal ion substitution may constitute a molecular basis for metal ion toxicity and/or metal-mediated functional control. The X-linked Inhibitor of Apoptosis Protein (XIAP) is a metalloprotein that requires zinc for proper structure and function. In addition to its role as a modulator of apoptosis, XIAP has been implicated in copper homeostasis. Given the similar coordination preferences of copper and zinc, investigation of XIAP structure and function upon interaction with copper is relevant. The Really Interesting New Gene (RING) domain of XIAP is representative of a class of zinc finger proteins that utilize a bi-nuclear zinc-binding motif to maintain proper structure and ubiquitin ligase function. Herein, we report the characterization of copper (I) binding to the Zn₂-RING domain of XIAP. Electronic absorption studies that monitor copper–thiolate interactions demonstrate that the RING domain of XIAP binds 5–6 Cu(I) ions and that copper is thermodynamically preferred relative to zinc. Repetition of the experiments in the presence of the Zn(II)-specific dye Mag-Fura2 shows that Cu(I) addition results in Zn(II) ejection from the protein, even in the presence of glutathione. Loss of dimeric structure of the RING domain, which is a requirement for its ubiquitin ligase activity, upon copper substitution at the zinc-binding sites, was readily observed via size exclusion chromatography. These results provide a molecular basis for the modulation of RING function by copper and add to the growing body of literature that describe the impact of Cu(I) on zinc metalloprotein structure and function.</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 5","pages":"485 - 494"},"PeriodicalIF":3.0,"publicationDate":"2023-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4089738","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}