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Journal of Inorganic Biochemistry
Elsevier Science Publishing Co.
Journal of Inorganic Biochemistry

Elsevier Science Publishing Co.

0162-0134

Journal of Inorganic Biochemistry/Journal Journal of Inorganic BiochemistrySCIISTPAHCI
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    Decavanadate interactions with the elements of the SARS-CoV-2 spike protein highlight the potential role of electrostatics in disrupting the infectivity cycle

    Favre D.Kaltashov I.A.Harmon J.F.Zhang A....
    5页
    查看更多>>摘要：? 2022 Elsevier Inc.Polyoxidometalates (POMs) exhibit a range of biological properties that can be exploited for a variety of therapeutic applications. However, their potential utility as antivirals has been largely overlooked in the ongoing efforts to identify safe, effective and robust therapeutic agents to combat COVID-19. We focus on decavanadate (V10), a paradigmatic member of the POM family, to highlight the utility of electrostatic forces as a means of disrupting molecular processes underlying the SARS-CoV-2 entry into the host cell. While the departure from the traditional lock-and-key approach to the rational drug design relies on less-specific and longer-range interactions, it may enhance the robustness of therapeutic agents by making them less sensitive to the viral mutations. Native mass spectrometry (MS) not only demonstrates the ability of V10 to associate with the receptor-binding domain of the SARS-CoV-2 spike protein, but also provides evidence that this association disrupts the protein binding to its host cell-surface receptor. Furthermore, V10 is also shown to be capable of binding to the polybasic furin cleavage site within the spike protein, which is likely to decrease the effectiveness of the proteolytic processing of the latter (a pre-requisite for the viral fusion with the host cell membrane). Although in vitro studies carried out with SARS-CoV-2 infected cells identify V10 cytotoxicity as a major factor limiting its utility as an antiviral agent, the collected data provide a compelling stimulus for continuing the search for effective, robust and safe therapeutics targeting the novel coronavirus among members of the POM family.
      原文链接:
    • NSTL
    • Elsevier

    Binding of ruthenium and osmium at non?iron sites of transferrin accounts for their iron-independent cellular uptake

    Wang H.Xu X.Lai T.-P.Wang M....
    5页
    查看更多>>摘要：? 2022 Elsevier Inc.Being identified with less toxic and generally showing selective effects for solid tumor metastases, ruthenium and osmium compounds are promising drug candidates for clinical uses. Human serum proteins, such as albumin and transferrin, play vital roles in the transportation and accumulation of ruthenium and osmium agents into target tissues. However, the molecular mechanism of how transferrin transport ruthenium and their osmium analogues at atomic level remains obscure. In this study, we uncovered that the cellular uptake of Os3+ or Ru3+ are not competed by Fe3+. To unveil the molecular mechanism behind the phenomena, we report the first crystal structures of human serum transferrin (hTF) in complex with ruthenium and osmium compounds bound to the non-conserved residues on the surface of hTF without altering its overall conformation. As for Ru3+ and Os3+, these binding sites by descending affinity are: His14/His289, His349–350 ~ His578/Arg581. Ruthenium drugs and their osmium analogues preferentially bind to His14/His289 with bipyridine or imidazole ligands leaving. These binding sites on hTF surface are also available in human lactoferrin and some transferrin family member of other species. The presence of these binding sites makes the cellular uptake of Ru3+ and Os3+ less affected by Fe3+, compare to Zr4+ or Hf4+. Collectively, these findings are critical for our understanding of the role of serum transferrin in cellular delivery of ruthenium and osmium anticancer agents.
      原文链接:
    • NSTL
    • Elsevier

    Biomimetic synthesis of L-DOPA inspired by tyrosine hydroxylase

    Du D.Su Y.Shang Q.Chen C....
    5页
    查看更多>>摘要：? 2022 Elsevier Inc.L-3,4-dihydroxyphenylalanine (L-DOPA) is in high demand as the cornerstone for treatment of Parkinson's disease. The current production of L-DOPA is associated with poor productivity and long production period. Biomimetic system inspired from tyrosine hydroxylase was developed to achieve the production of L-DOPA from tyrosine with high reactivity, efficiency, and specificity. The biomimetic system owned close resemblance of component and structure in comparison with tyrosine hydroxylase, consisting of tyrosine as substrate, a redox complex of Fe2+ and EDTA as the catalyst to simulate the active center of the natural tyrosine hydroxylase, hydrogen peroxide as the oxidant, and ascorbic acid as the reductant. HPLC, HPLC-MS/MS, 1H NMR, and specific rotation identified L-DOPA was generated. The system showed high catalytic activity and regioselectivity for hydroxylation of tyrosine as equal to tyrosine hydroxylase. FeIVO2+ was formed as the major active species, and NIH shift was observed. EDTA accelerated the reaction by reducing the redox potential of Fe3+/Fe2+ couple. Density functional theory calculation suggested formation of FeIVO2+ was more thermodynamically favorable. The biomimetic system shared analogous catalytic mechanism with TyrH. Process parameters was optimized for maximum production of L-DOPA, namely 6.4 mM tyrosine, 1.6 mM Fe2+, 1.92 mM EDTA, 150 mM H2O2, and 35 mM ascorbic acid in 0.2 M glycine-HCl buffer at pH 4.5 and 60 °C. The yield, titer, and productivity were obtained as 52.01%, 3.22 mM, and 48,210.68 mg L?1 h?1, respectively. The proposed method exhibited an amazing productivity, might provide a promising strategy to industrialize L-DOPA production.
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    • NSTL
    • Elsevier

    Corrigendum to “Toxicological mechanism of large amount of copper supplementation: Effects on endoplasmic reticulum stress and mitochondria-mediated apoptosis by Nrf2/HO-1 pathway-induced oxidative stress in the porcine myocardium” [J. Inorg. Biochem. 230 (2022), 111750] (Journal of Inorganic Biochemistry (2022) 230, (S0162013422000393), (10.1016/j.jinorgbio.2022.111750))

    Li Q.Liao J.Zhang K.Hu Z....
    5页
    查看更多>>摘要：? 2022The authors regret the error in Fig. 2C of the published article. The correct and final version of Fig. 2 is as follows. These corrections do not alter any of the conclusions of the article. The authors would like to apologise for any inconvenience caused.
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    On the reactions of Cu(II/I)ATP complexes with methyl radicals

    Kornweitz H.Saphier M.Yardeni G.Lerner A....
    5页
    查看更多>>摘要：? 2022The CuI/IIATP react with methyl radicals to form methane and methanol, where CuIATP reacts with ?CH3 in a process that is surprisingly slow. The low-rate constant of this process is attributed to the significant rearrangement of the chelating ligand required for the transient's formation. These results were corroborated by DFT calculations of the relevant compounds.
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    • NSTL
    • Elsevier

    The molybdenum storage protein forms and deposits distinct polynuclear tungsten oxygen aggregates

    Aziz I.Kayastha K.Khera R.Ermler U....
    5页
    查看更多>>摘要：? 2022Some N2-fixing bacteria store Mo to maintain the formation of the vital FeMo-cofactor dependent nitrogenase under Mo depleting conditions. The Mo storage protein (MoSto), developed for this purpose, has the unique capability to compactly deposit molybdate as polyoxometalate (POM) clusters in a (αβ)3 hexameric cage; the same occurs with the physicochemically related tungstate. To explore the structural diversity of W-based POM clusters, MoSto loaded under different conditions with tungstate and two site-specifically modified MoSto variants were structurally characterized by X-ray crystallography or single-particle cryo-EM. The MoSto cage contains five major locations for POM clusters occupied among others by heptanuclear, Keggin ion and even Dawson-like species also found in bulk solvent under defined conditions. We found both lacunary derivatives of these archetypical POM clusters with missing WOx units at positions exposed to bulk solvent and expanded derivatives with additional WOx units next to protecting polypeptide segments or other POM clusters. The cryo-EM map, unexpectedly, reveals a POM cluster in the cage center anchored to the wall by a WOx linker. Interestingly, distinct POM cluster structures can originate from identical, highly occupied core fragments of three to seven WOx units that partly correspond to those found in MoSto loaded with molybdate. These core fragments are firmly bound to the complementary protein template in contrast to the more variable, less occupied residual parts of the visible POM clusters. Due to their higher stability, W-based POM clusters are, on average, larger and more diverse than their Mo-based counterparts.
      原文链接:
    • NSTL
    • Elsevier

    NMR of paramagnetic metalloproteins in solution: Ubi venire, quo vadis?

    Trindade I.B.Coelho A.Louro R.O.Cantini F....
    5页
    查看更多>>摘要：? 2022Metalloproteins represent a substantial fraction of the proteome where they have an outsized contribution to enzymology. This stems from the reactivity of transition metals found in the active sites of numerous classes of enzymes that undergo redox and/or spin-state transitions. Notwithstanding, NMR structures of metalloproteins deposited in the PDB are under-represented and NMR studies exploring paramagnetic states are a minute fraction of the overall database content. This state of affairs contrasts with the early recognition that paramagnetic proteins offer unique opportunities for structure-function studies which are not available for diamagnetic proteins. Recent development of novel pulse sequences that minimize quenching of signal intensity that arises from the presence of a paramagnetic center in metalloproteins is extending even further the range of systems which can be studied by solution-state NMR. In this manuscript we review solution-state NMR applications to paramagnetic proteins, highlighting the developments in both methodologies and data interpretation, laying bare the vast range of opportunities for paramagnetic NMR to contribute to the understanding of structure and function of metalloenzymes and biomimetic metallocatalysts.
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    • NSTL
    • Elsevier

    Metformin attenuates cadmium-induced degeneration of spiral ganglion neuron via restoring autophagic flux in primary culture

    Li Q.Wang L.Ji D.Yu W....
    5页
    查看更多>>摘要：? 2022 Elsevier Inc.Cadmium (Cd), a common environmental and occupational toxicant, is an important risk factor for hearing loss. After exposure, Cd accumulates in the inner ear and induces spiral ganglion neuron (SGN) degeneration; however, the underlying mechanisms are poorly understood. Dysfunctional autophagy has been implicated in many neurodegenerative diseases, including Cd-induced neurotoxicity. Metformin has been validated to confer not only anti-hyperglycaemic but also neuroprotective effects. However, the relationship between autophagy dysfunction, SGN degeneration, and the effect of metformin on Cd-induced SGN neurotoxicity has not yet been established. In this study, we demonstrate that metformin notably attenuates Cd-evoked SGN degeneration by restoring impaired autophagy flux, as evidenced by the suppression of Cd-induced elevation of autophagy markers microtubule-associated protein 1A/1B-light chain 3-II (LC3-II) and autophagy substrate protein p62 in degenerated SGN. Blockage of autophagy flux by chloroquine abolished metformin-induced neuroprotection against Cd-induced neurotoxicity in SGN. The results of this study reveal that autophagy dysfunction is an important component of Cd-induced SGN degeneration, and metformin may be a potential protective agent for attenuating SGN degeneration following Cd exposure.
      原文链接:
    • NSTL
    • Elsevier

    Polypyridyl ruthenium complexes as bifunctional TAR RNA binders and HIV-1 reverse transcriptase inhibitors

    Guo Y.-X.Liu M.Zhang H.Gao F....
    5页
    查看更多>>摘要：? 2022 Elsevier Inc.Inhibitors of type 1 human immunodeficiency virus (HIV-1) reverse transcriptase are central to anti-HIV therapy. Most of their targets are enzymes, while very few could bind to viral RNA. Here we designed four new polypyridyl Ru(II) complexes, which could bind HIV-1 TAR RNA tightly and selectively by molecular recognition of hydrogen bonds, further stabilize the Ru(II)-RNA bound system by electrostatic attraction, and efficiently inhibit the Moloney murine leukemia virus (M-MuLV) and HIV-1 reverse transcriptase. The polypyridyl Ru(II) complexes also have physical and chemical advantages, including high chemical stability and photostability, sensitive spectroscopic responses to HIV TAR RNA, and low toxicity to normal cells. This work also provides valuable drug design strategies for acquired immune deficiency syndrome (AIDS) and other reverse transcriptase related disease research, such as hepatitis C virus (HCV), Ebola virus (EBOV), influenza A virus, and most recently the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
      原文链接:
    • NSTL
    • Elsevier

    Tuning reduction potentials of type 1 copper center in azurin by replacing a histidine ligand with its isostructural analogues

    Yu Y.Lu Y.Marshall N.M.Garner D.K....
    5页
    查看更多>>摘要：? 2022 Elsevier Inc.Type 1 copper proteins have a conserved ligand set of one cysteine and two histidines, with many proteins, such as azurin, also containing an axial methionine. While the cysteine and methionine in azurin have been replaced with their respective isostructural analogues of unnatural amino acids to reveal their roles in tuning electronic structures and functional properties, such as reduction potentials (E°′), the histidine ligands have not been probed in this way. We herein report the substitution of His117 in azurin with three unnatural isostructural analogues, 5-nitrohistidine(Ntr), thiazolylalanine(SHis) and 1-methylhistidine(MeH) by expressed protein ligation. While UV–vis absorption and electron paramagnetic resonance spectroscopies confirm that isostructural replacement results in minimal structural change in the Cu(II) state, the E°′ of these variants increases with increasing pKa of the δ nitrogens of the imidazole. This counter-intuitive relationship between E°′ of the protein and pKa of the sidechain group suggests additional factors may play a role in tuning E°′.
      原文链接:
    • NSTL
    • Elsevier