Journal of Inorganic Biochemistry最新文献

{"title":"Effect of CO binding to P450 BM3 F393 mutants on electron density distribution in the heme cofactor","authors":"Johannes P.M. Schelvis ,&nbsp;Zhucheng Chen ,&nbsp;Marisa A. Messina ,&nbsp;Jaclyn Catalano","doi":"10.1016/j.jinorgbio.2024.112660","DOIUrl":"10.1016/j.jinorgbio.2024.112660","url":null,"abstract":"<div><p>Resonance Raman spectroscopy has been performed on a set of cytochrome P450 BM3 heme domains in which mutation of the highly conserved Phe393 induces significant variation in heme iron reduction potential. In previous work [Chen, Z., Ost, T.W.B., and Schelvis, J.P.M. (2004) <em>Biochemistry</em> 43, 1798–1808], a correlation between heme vinyl conformation and the heme iron reduction potential indicated a steric control by the protein over the distribution of electron density in the reduced heme cofactor. The current study aims to monitor changes in electron density on the ferrous heme cofactor following CO binding. In addition, ferric-NO complexes have been studied to investigate potential changes to the proximal Cys400 thiolate. We find that binding of CO to the ferrous heme domains results in a reorientation of the vinyl groups to a largely out-of-plane conformation, the extent of which correlates with the size of the residue at position 393. We conclude that Fe^II d_π back bonding to the CO ligand largely takes away the need for conjugation of the vinyl groups with the porphyrin ring to accommodate Fe^II d_π back bonding to the porphyrin ligand. The ferrous-CO and ferric-NO data are consistent with a small decrease in σ-electron donation from the proximal Cys400 thiolate in the F393A mutant and, to a lesser extent, the F393H mutant, potentially due to a small increase in hydrogen bonding to the proximal ligand. Phe393 seems strategically placed to preserve robust σ-electron donation to the heme iron and to fine-tune its electron density by limiting vinyl group rotation.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into the antineoplastic activity and mechanisms of action of coumarin-coordinated 8-hydroxyquinoline ruthenium(II/III) compounds","authors":"Ling-Qi Du ,&nbsp;Yan Yang ,&nbsp;Li Ruan ,&nbsp;Song Sun ,&nbsp;Dong-Yin Mo ,&nbsp;Jin-Yuan Cai ,&nbsp;Hong Liang ,&nbsp;Sai Shu ,&nbsp;Qi-Pin Qin","doi":"10.1016/j.jinorgbio.2024.112659","DOIUrl":"10.1016/j.jinorgbio.2024.112659","url":null,"abstract":"<div><p>Ruthenium(II/III) coordination compounds have gained widespread attention as chemotherapy drugs, photosensitizers, and photodynamic therapy reagents. Herein, a family of 11 novel coumarin-coordinated 8-hydroxyquinoline ruthenium(II/III) compounds, i.e., [Ru^II₂(<em>μ</em>₂-Cl)₂(QL1a)₂(DMSO)₄] (<strong>YNU-4a</strong> = Yulin Normal University-4a), [Ru^II₂(<em>μ</em>₂-Cl)₂(QL1b)₂(DMSO)₄] (<strong>YNU-4b</strong>), [Ru^II₂(<em>μ</em>₂-Cl)₂(QL1c)₂(DMSO)₄] (<strong>YNU-4c</strong>), [Ru^II₂(<em>μ</em>₂-Cl)₂(QL1d)₂(DMSO)₄]⋅2CH₃OH (<strong>YNU-4d</strong>), [Ru^II(QL1e)₂(DMSO)₂] (<strong>YNU-4e</strong>), [Ru^III(QL1e)₂(QL3a)] (<strong>YNU-4f</strong>), [Ru^III(QL1e)₂(QL3b)] (<strong>YNU-4g</strong>), [Ru^III(QL1e)₂(QL3c)] (<strong>YNU-4h</strong>), [Ru^IICl₂(H-QL3a)₂(DMSO)₂] (<strong>YNU-4i</strong>), [Ru^IICl₂(H-QL3b)₂(DMSO)₂] (<strong>YNU-4j</strong>), and [Ru^IICl₂(H-QL3c)₂(DMSO)₂] (<strong>YNU-4k</strong>), featuring the coligands 5,7-diiodo-8-hydroxyquinoline (H-QL1a), 5,7-dichloro-8-quinolinol (H-QL1b), 5-chloro-7-iodo-8-hydroxyquinolin (H-QL1c), 5,7-dibromo-8-hydroxyquinoline (H-QL1d), and 5,7-dichloro-8-hydroxy-2-methylquinoline (H-QL1e) and the main ligands 6,7-dichloro-3-pyridin-2-yl-chromen-2-one (H-QL3a), 6-bromo-3-pyridin-2-yl-chromen-2-one (H-QL3b), and 6-chloro-3-pyridin-2-yl-chromen-2-one (H-QL3c), respectively. The structure of compounds <strong>YNU-4a</strong>–<strong>YNU-4k</strong> was fully confirmed by conducting various spectroscopic analyses. The anticancer activity of <strong>YNU-4a</strong>–<strong>YNU-4k</strong> was evaluated in cisplatin-resistant A549/DDP lung cancer cells (LC549) versus normal embryonic kidney (HEK293) cells. Notably, compound <strong>YNU-4f</strong> bearing QL1e and QL3a ligands showed a more pronounced antiproliferative effect against LC549 cells (IC₅₀ = 1.75 ± 0.09 μM) with high intrinsic selectivity toward LC549 cancer cells than <strong>YNU-4a</strong>–<strong>YNU-4e</strong>, H-QL1a–H-QL1e, cisplatin (PDD), <strong>YNU-4g</strong>–<strong>YNU-4k</strong>, and H-QL3a–H-QL3c. Additionally, a colocalization assay analysis of <strong>YNU-4e</strong> and <strong>YNU-4f</strong> showed that these two ruthenium(II/III) compounds were subcellularly accumulated in the mitochondria and other regions of the cytoplasm, where they induce mitophagy, adenosine triphosphate (ATP) reduction, mitochondrial respiratory chain complex I/IV(RC1/RC4) inhibition, and mitochondrial dysfunction. Accordingly, compounds <","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probing conformational dynamics of DNA binding by CO-sensing transcription factor, CooA","authors":"Madeleine G. Roberts ,&nbsp;Matthew R. Dent ,&nbsp;Sashary Ramos ,&nbsp;Megan C. Thielges ,&nbsp;Judith N. Burstyn","doi":"10.1016/j.jinorgbio.2024.112656","DOIUrl":"10.1016/j.jinorgbio.2024.112656","url":null,"abstract":"<div><p>The transcription factor CooA is a CRP/FNR (cAMP receptor protein/ fumarate and nitrate reductase) superfamily protein that uses heme to sense carbon monoxide (CO). Allosteric activation of CooA in response to CO binding is currently described as a series of discrete structural changes, without much consideration for the potential role of protein dynamics in the process of DNA binding. This work uses site-directed spin-label electron paramagnetic resonance spectroscopy (SDSL-EPR) to probe slow timescale (μs-ms) conformational dynamics of CooA with a redox-stable nitroxide spin label, and IR spectroscopy to probe the environment at the CO-bound heme. A series of cysteine substitution variants were created to selectively label CooA in key functional regions, the heme-binding domain, the 4/5-loop, the hinge region, and the DNA binding domain. The EPR spectra of labeled CooA variants are compared across three functional states: Fe(III) “locked off”, Fe(II)-CO “on”, and Fe(II)-CO bound to DNA. We observe changes in the multicomponent EPR spectra at each location; most notably in the hinge region and DNA binding domain, broadening the description of the CooA allosteric mechanism to include the role of protein dynamics in DNA binding. DNA-dependent changes in IR vibrational frequency and band broadening further suggest that there is conformational heterogeneity in the active WT protein and that DNA binding alters the environment of the heme-bound CO.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Fe(III) coordination and membrane interaction of a siderophore-peptide conjugate: Enhancing synergistically the antimicrobial activity","authors":"Rosa Bellavita ,&nbsp;Simone Braccia ,&nbsp;Lorenzo Emiliano Imbò ,&nbsp;Paolo Grieco ,&nbsp;Stefania Galdiero ,&nbsp;Gabriella D'Auria ,&nbsp;Annarita Falanga ,&nbsp;Lucia Falcigno","doi":"10.1016/j.jinorgbio.2024.112658","DOIUrl":"10.1016/j.jinorgbio.2024.112658","url":null,"abstract":"<div><p>Many microbes produce siderophores, which are extremely potent weapons capable of stealing iron ions from human tissues, fluids and cells and transferring them into bacteria through their appropriate porins. We have recently designed a multi-block molecule, each block having a dedicated role. The first component is an antimicrobial peptide, whose good effectiveness against some bacterial strains was gradually improved through interactive sequence modifications. Connected to this block is a flexible bio-band, also optimized in length, which terminates in a hydroxyamide unit, a strong metal binder. Thus, the whole molecule brings together two pieces that work synergistically to fight infection. To understand if the peptide unit, although modified with a long tail, preserves the structure and therefore the antimicrobial activity, and to characterize the mechanism of interaction with bio-membrane models mimicking Gram-negative membranes, we performed a set of fluorescence-based experiments and circular dichroism studies, which further supported our design of a combination of two different entities working synergistically. The chelating activity and iron(III) binding of the peptide was confirmed by iron(III) paramagnetic NMR analyses, and through a competitive assay with ethylenediamine-tetra acetic acid by ultraviolet–visible spectroscopy. The complexation parameters, the Michaelis constant K, and the number of sites n, evaluated with spectrophotometric techniques are confirmed by Fe(III) paramagnetic NMR analyses here reported. In conclusion, we showed that the coupling of antimicrobial capabilities with iron-trapping capabilities works well in the treatment of infectious diseases caused by Gram-negative pathogens.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S016201342400182X/pdfft?md5=5dea132cb3543cfbd1f8b0a7c8931150&pid=1-s2.0-S016201342400182X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photo-induced imine reduction by a photoredox biocatalyst consisting of a pentapeptide and a Ru bipyridine terpyridine complex","authors":"Ryusei Kano ,&nbsp;Koji Oohora ,&nbsp;Takashi Hayashi","doi":"10.1016/j.jinorgbio.2024.112657","DOIUrl":"10.1016/j.jinorgbio.2024.112657","url":null,"abstract":"<div><p>Imine reduction is a useful reaction in the preparation of amine derivatives. Various catalysts have been reported to promote this reaction and photoredox catalysts are promising candidates for sustainable amine synthesis. Improvement of this reaction using biomolecule-based reaction scaffolds is expected to increase the utility of the reaction. In this context, we have recently investigated photoredox Ru complexes with pentapeptide scaffolds <em>via</em> coordination bonds as catalysts for photoreduction of dihydroisoquinoline derivatives. First, Ru bipyridine terpyridine complexes coordinated with five different pentapeptides (XVHVV: X = V, F, W, Y, C) were prepared and characterized by mass spectrometry. Catalytic activities of the Ru complexes with XVHVV were evaluated for photoreduction of dihydroisoquinoline derivatives in the presence of ascorbate and thiol compounds as sacrificial reagents and hydrogen sources. Interestingly, the turnover number of the Ru complex with VVHVV is 531, which is two-fold higher than that of a simple Ru complex with an imidazole ligand. The detailed emission lifetime measurements indicate that the enhanced catalytic activity provided by the peptide scaffold is caused by an efficient reaction with the thiol derivative to accelerate reductive quenching of Ru complex. The quenching behavior suggests formation of an active species such as a Ru(I) complex. These findings reveal that the simple pentapeptide serves as an effective scaffold to enhance the photocatalytic activity of a photoactive Ru complex.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0162013424001818/pdfft?md5=601769008a9f862af456c8161c611db7&pid=1-s2.0-S0162013424001818-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria- and endoplasmic reticulum-localizing iridium(III) complexes induce immunogenic cell death of 143B cells","authors":"Yuqing Zhang ,&nbsp;Yao Gong ,&nbsp;Zhijun Liang ,&nbsp;Wei Wu ,&nbsp;Jiaxi Chen ,&nbsp;Yuling Li ,&nbsp;Rui Chen ,&nbsp;Jun Mei ,&nbsp;Zunnan Huang ,&nbsp;Jing Sun","doi":"10.1016/j.jinorgbio.2024.112655","DOIUrl":"10.1016/j.jinorgbio.2024.112655","url":null,"abstract":"<div><p>Recent breakthroughs in cancer immunology have propelled immunotherapy to the forefront of cancer research as a promising treatment approach that harnesses the body's immune system to effectively identify and eliminate cancer cells. In this study, three novel cyclometalated Ir(III) complexes, <strong>Ir1</strong>, <strong>Ir2</strong>, and <strong>Ir3</strong>, were designed, synthesized, and assessed <em>in vitro</em> for cytotoxic activity against several tumor-derived cell lines. Among these, <strong>Ir1</strong> exhibited the highest cytotoxic activity, with an IC₅₀ value of 0.4 ± 0.1 μM showcasing its significant anticancer potential. Detailed mechanistic analysis revealed that co-incubation of <strong>Ir1</strong> with 143B cells led to <strong>Ir1</strong> accumulation within mitochondria and the endoplasmic reticulum (ER). Furthermore, <strong>Ir1</strong> induced G0/G1 phase cell cycle arrest, while also diminishing mitochondrial membrane potential, disrupting mitochondrial function, and triggering ER stress. Intriguingly, in mice the <strong>Ir1</strong>-induced ER stress response disrupted calcium homeostasis to thereby trigger immunogenic cell death (ICD), which subsequently activated the host antitumor immune response while concurrently dampening the <em>in vivo</em> tumor-induced inflammatory response.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heme d formation in a Shewanella benthica hemoglobin","authors":"Jaime E. Martinez Grundman ,&nbsp;Thomas D. Schultz ,&nbsp;Jamie L. Schlessman ,&nbsp;Kevin Liu ,&nbsp;Eric A. Johnson ,&nbsp;Juliette T.J. Lecomte","doi":"10.1016/j.jinorgbio.2024.112654","DOIUrl":"10.1016/j.jinorgbio.2024.112654","url":null,"abstract":"<div><p>In our continued investigations of microbial globins, we solved the structure of a truncated hemoglobin from <em>Shewanella benthica</em>, an obligate psychropiezophilic bacterium. The distal side of the heme active site is lined mostly with hydrophobic residues, with the exception of a tyrosine, Tyr34 (CD1) and a histidine, His24 (B13). We found that purified SbHbN, when crystallized in the ferric form with polyethylene glycol as precipitant, turned into a green color over weeks. The electron density obtained from the green crystals accommodated a <em>trans</em> heme <em>d</em>, a chlorin-type derivative featuring a γ-spirolactone and a vicinal hydroxyl group on a pyrroline ring. In solution, exposure of the protein to one equivalent of hydrogen peroxide resulted in a similar green color change, but caused by the formation of multiple products. These were oxidation species released on protein denaturation, likely including heme <em>d</em>, and a species with heme covalently attached to the polypeptide. The Tyr34Phe replacement prevented the formation of both heme <em>d</em> and the covalent linkage. The ready modification of heme <em>b</em> by SbHbN expands the range of chemistries supported by the globin fold and offers a route to a novel heme cofactor.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The fully reduced terminal oxidase bd-I isolated from Escherichia coli binds cyanide","authors":"Vitaliy B. Borisov ,&nbsp;Alexander M. Arutyunyan","doi":"10.1016/j.jinorgbio.2024.112653","DOIUrl":"10.1016/j.jinorgbio.2024.112653","url":null,"abstract":"<div><p>Cytochrome <em>bd</em>-I from <em>Escherichia coli</em> belongs to the superfamily of prokaryotic <em>bd</em>-type oxygen reductases. It contains three hemes, <em>b</em>₅₅₈, <em>b</em>₅₉₅ and <em>d</em>, and couples oxidation of quinol by dioxygen with the generation of a proton-motive force. The enzyme exhibits resistance to various stressors and is considered as a target protein for next-generation antimicrobials. By using electronic absorption and MCD spectroscopy, this work shows that cyanide binds to heme <em>d</em>²⁺ in the isolated fully reduced cytochrome <em>bd</em>-I. Cyanide-induced difference absorption spectra display changes near the heme <em>d</em>²⁺ α-band, a minimum at 633 nm and a maximum around 600 nm, and a W-shaped response in the Soret region. Apparent dissociation constant (<em>K</em>_d) of the cyanide complex of heme <em>d</em>²⁺ is ∼0.052 M. Kinetics of cyanide binding is monophasic, indicating the presence of a single ligand binding site in the enzyme. Consistently, MCD data show that cyanide binds to heme <em>d</em>²⁺ but not to <em>b</em>₅₅₈²⁺ or <em>b</em>₅₉₅²⁺. This agrees with the published structural data that the enzyme's active site is not a di-heme site. The observed rate of binding (<em>k</em>_obs) increases as the concentration of cyanide is increased, giving a second-order rate constant (<em>k</em>_on) of ∼0.1 M⁻¹ s⁻¹.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"White light increases anticancer effectiveness of iridium(III) complexes toward lung cancer A549 cells","authors":"Gechang Li ,&nbsp;Jing Chen ,&nbsp;Yufeng Xie ,&nbsp;Yan Yang ,&nbsp;Yajie Niu ,&nbsp;Xiaolan Chen ,&nbsp;Xiandong Zeng ,&nbsp;Lin Zhou ,&nbsp;Yunjun Liu","doi":"10.1016/j.jinorgbio.2024.112652","DOIUrl":"10.1016/j.jinorgbio.2024.112652","url":null,"abstract":"<div><p>Anticancer activity has been extensively studies. In this article, three ligands 2-(6-bromobenzo[d][1,3]dioxol-5-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (BDIP), 2-(7-methoxybenzo[d][1,3]dioxol-5-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (MDIP), 2-(6-nitrobenzo[d][1,3]dioxol-5-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (NDIP) and their iridium(III) complexes: [Ir(ppy)₂(BDIP)](PF₆) (ppy = deprotonated 2-phenylpyridine, 3a), [Ir(ppy)₂(MDIP)](PF₆) (3b) and [Ir(ppy)₂(NDIP)](PF₆) (3c) were synthesized. The cytotoxicity of 3a, 3b, 3c against Huh7, A549, BEL-7402, HepG2, HeLa, and non-cancer NIH3T3 was tested using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. The results obtained from the MTT test stated clearly that these complexes demonstrated moderate or non-cytotoxicity toward Huh7, BEL-7402, HepG2 and HeLa except A549 cells. To improve the anticancer efficacy, we used white light to irradiate the mixture of cells and complexes for 30 min, the anticancer activity of the complexes was greatly enhanced. Particularly, 3a and 3b exhibited heightened capability to inhibit A549 cells proliferation with IC₅₀ (half maximal inhibitory concentration) values of 0.7 ± 0.3 μM and 1.8 ± 0.1 μM, respectively. Cellular uptake has shown that 3a and 3b can be accumulated in the cytoplasm. Wound healing and colony forming showed that 3a and 3b significantly hinder the cell migration and growth in the S phase. The complexes open mitochondrial permeability transition pore (MPTP) channel and cause the decrease of membrane potential, release of cytochrome C, activation of caspase 3, and finally lead to apoptosis. In addition, 3a and 3b cause autophagy, increase the lipid peroxidation and lead to ferroptosis. Also, 3a and 3b increase the expression of calreticulin (CRT), high mobility group box 1 (HMGB1), heat shock protein 70 (HSP70), thereby inducing immunogenic cell death.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theoretical insights into the reduction of Azurin metal site with unnatural amino acid substitutions","authors":"Yang Wei,&nbsp;Pengfei Li","doi":"10.1016/j.jinorgbio.2024.112651","DOIUrl":"10.1016/j.jinorgbio.2024.112651","url":null,"abstract":"<div><p>Copper-containing proteins play crucial roles in biological systems. Azurin is a copper-containing protein which has a Type 1 copper site that facilitates electron transfer in the cytochrome chain. Previous research has highlighted the significant impact of mutations in the axial Met121 of the copper site on the reduction potential. However, the mechanism of this regulation has not been fully established. In this study, we employed theoretical modeling to investigate the reduction of the Type 1 copper site, focusing on how unnatural amino acid substitutions at Met121 influence its behavior. Our findings demonstrated a strong linear correlation between electrostatic interactions and the reduction potential of the copper site, which indicates that the perturbation of the reduction potential is primarily influenced by electrostatic interactions between the metal ion and the ligating atom. Furthermore, we found that CF/π and CF…H interactions could induce subtle changes in geometry and hence impact the electronic properties of the systems under study. In addition, our calculations suggest the coordination mode and ion-ligand distance could significantly impact the reduction potential of a copper site. Overall, this study offers valuable insights into the structural and electronic properties of the Type 1 copper site, which could potentially guide the design of future artificial catalysts.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}