Journal of Inorganic Biochemistry最新文献

{"title":"P450 Electron transfer: Towards in vitro NAD(P)H-independent biocatalysis","authors":"Olivia Paredes,&nbsp;Ava Arabshahi,&nbsp;Jacqueline Hu,&nbsp;Neel Kumar,&nbsp;Vikram Shende,&nbsp;Michael G. Hill,&nbsp;Andrew K. Udit","doi":"10.1016/j.jinorgbio.2025.113100","DOIUrl":"10.1016/j.jinorgbio.2025.113100","url":null,"abstract":"<div><div>Oxidation reactions have been studied extensively as their applications are broad, spanning pharmaceuticals, textiles, and fine chemicals. Such reactions can be challenging to perform, particularly on relatively inert C-H bonds; regio- and stereospecificity, as well as overall molecular integrity can be difficult to maintain given the harsh conditions that may be needed. Biocatalysis with cytochromes P450 (P450s) provides a solution to these challenges: a key requirement is providing the enzymes with the necessary reducing equivalents, which naturally comes from NAD(<em>P</em>)H. The complexity of either replicating in vivo systems or providing an enzymatic cofactor recycling system suggests that in vitro, NAD(<em>P</em>)H-independent systems may be a preferred approach, simplifying the system to the key components. Towards this, electrochemical methods have featured prominently, and photochemical approaches have also recently been established as a viable alternative. For those systems that do not utilize a reductase, some mechanistic understanding of the electron transfer involved is critical for achieving native-like catalysis. This focused review tracks the development of these systems, with key examples and findings along the way that lead to a selection of the more recent approaches discussed herein.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"275 ","pages":"Article 113100"},"PeriodicalIF":3.2,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145359941","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":"Antilung cancer activity and apoptosis mechanisms of imidazolyl acylhydrazone zinc and europium complexes with chain structures","authors":"Xiaotong Lu ,&nbsp;Pan Zhang ,&nbsp;Zijie Zhao,&nbsp;Yaqing Xie,&nbsp;Shouying Cao,&nbsp;Minglun Liu,&nbsp;Lili Liang","doi":"10.1016/j.jinorgbio.2025.113118","DOIUrl":"10.1016/j.jinorgbio.2025.113118","url":null,"abstract":"<div><div>In this study, a novel bidentate imidazolyl acylhydrazone ligand containing an imidazolyl group was designed, and two novel complexes [ZnL(CH₃OH)]·NO₃ (<strong>1</strong>) and [EuL(NO₃)₂DMF] (<strong>2</strong>) with a 1D chain structure were synthesized as expected, which shows significantly stronger anti-lung cancer activity than cisplatin. Complexes <strong>1</strong> and <strong>2</strong> effectively inhibit A549 cell proliferation by up-regulating the expression of cytochrome C, cleaved-caspase 3, and Bax, while down-regulating Pro-caspase 3 and Bcl-2 expression, thereby suppressing cell cycle progression and inducing the classical apoptotic pathway. Additionally, these complexes significantly inhibit A549 cell migration. Furthermore, they further elevate intracellular reactive oxygen species (ROS) levels and reduce mitochondrial membrane potential in A549 cells. <em>In vivo</em> anti-tumor evaluations show that complexes <strong>1</strong> and <strong>2</strong> significantly outperform cisplatin in inhibiting the growth of A549 subcutaneous tumors in nude mice, with no apparent damage to major organs. The results of histological examination show that complexes <strong>1</strong> and <strong>2</strong> do not cause obviously pathological damage to the main organs, which further verify their good biosafety <em>in vivo</em>. This study provides a research basis for the research and development of new metal-based drugs with chain structures which show high efficiency and low toxicity.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"275 ","pages":"Article 113118"},"PeriodicalIF":3.2,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145317982","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":"Hydroxy-substituted electron deficient Pd porphyrin cofactors illuminate ultrafast proton transfer reactions","authors":"Jiaqi Zhu ,&nbsp;Rui Liu ,&nbsp;Jarrett P. Mansergh ,&nbsp;Minting Ouyang ,&nbsp;Lindsay R. Pederson ,&nbsp;Ian Bakanas ,&nbsp;William F. DeGrado ,&nbsp;Michael J. Therien","doi":"10.1016/j.jinorgbio.2025.113116","DOIUrl":"10.1016/j.jinorgbio.2025.113116","url":null,"abstract":"<div><div>Coordinated electron and proton movement drive bioenergetic functions. Relative to electron transfer reactions, tracking proton transport over fast-to-ultrafast time scales is challenging. Optical resolution of proton transfer dynamics can take advantage of chromophoric photoacids that not only trigger proton migration upon photoexcitation, but produce distinct spectroscopic changes associated with protonation/deprotonation. In this work, we report the design of a hydroxy-substituted electron deficient Pd porphyrin, <strong>PPd(C</strong>_{<strong>6</strong>}<strong>F</strong>_{<strong>5</strong>}<strong>)</strong>_{<strong>3</strong>}<strong>OH</strong>; upon photoexcitation, the acidity constant of this weak acid (p<em>K</em>a = 6.49) dramatically drops (p<em>K</em>a* = 0.97). Electronic excitation of <strong>PPd(C</strong>_{<strong>6</strong>}<strong>F</strong>_{<strong>5</strong>}<strong>)</strong>_{<strong>3</strong>}<strong>OH</strong> triggers an ultrafast proton transfer reaction (<strong>PPd(C</strong>_{<strong>6</strong>}<strong>F</strong>_{<strong>5</strong>}<strong>)</strong>_{<strong>3</strong>}<strong>OH</strong> +:B + hυ → ^{<strong>1</strong>}<strong>[PPd(C</strong>_{<strong>6</strong>}<strong>F</strong>_{<strong>5</strong>}<strong>)</strong>_{<strong>3</strong>}<strong>OH]*</strong> +:B → ^{<strong>1</strong>}<strong>[PPd(C</strong>_{<strong>6</strong>}<strong>F</strong>_{<strong>5</strong>}<strong>)</strong>_{<strong>3</strong>}<strong>O]</strong>^{<strong>−</strong>}<strong>*</strong> + HB^{<strong>+</strong>}; τ_PT = 342 fs) to a H-bonded base (B) in solution. Both <strong>PPd(C</strong>_{<strong>6</strong>}<strong>F</strong>_{<strong>5</strong>}<strong>)</strong>_{<strong>3</strong>}<strong>OH</strong> and its conjugate anion <strong>PPd(C</strong>_{<strong>6</strong>}<strong>F</strong>_{<strong>5</strong>}<strong>)</strong>_{<strong>3</strong>}<strong>O</strong>^{<strong>−</strong>} exhibit distinct vis-NIR spectral features for their respective ground and excited states. Because the electroni-cally excited triplet lifetimes of these species exceed tens of microseconds, the <strong>PPd(C</strong>_{<strong>6</strong>}<strong>F</strong>_{<strong>5</strong>}<strong>)</strong>_{<strong>3</strong>}<strong>OH</strong> photoacid defines an ideal cofactor to probe light-triggered proton release and track long-range proton migration in protein environments.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"275 ","pages":"Article 113116"},"PeriodicalIF":3.2,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145359914","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 cytochrome P450 decarboxylase from Staphylococcus aureus can produce a diene from a C18 monounsaturated fatty acid: A spectroscopic, structural and kinetic characterisation","authors":"Lewis J. Williams ,&nbsp;Michael T. Wilson ,&nbsp;James A. Birrell ,&nbsp;Harry W. Lang ,&nbsp;Stephen G. Bell ,&nbsp;Jonathan A.R. Worrall","doi":"10.1016/j.jinorgbio.2025.113117","DOIUrl":"10.1016/j.jinorgbio.2025.113117","url":null,"abstract":"<div><div>Certain members of the bacterial cytochrome P450 152 family (CYP152) are peroxygenases that catalyse the decarboxylation of fatty acids into terminal olefins making them attractive biocatalysts for biofuel production. To date, the characterisation of decarboxylating CYP152s has mainly focused on their reaction with saturated fatty acid substrates. CYP152s are often co-purified with a bound substrate, which is generally removed before further experiments are conducted. In the present work we identified that heterologous over-expressed CYP152 from <em>Staphylococcus aureus</em> (OleT_Sa) is co-purified with the <em>trans</em>-monounsaturated C_18:1 fatty acid, elaidic acid. We report the spectral, thermodynamic and kinetic characteristics of OleT_Sa bound to both elaidic acid and its saturated counterpart, stearic acid. Despite differing spectral profiles, metabolic and kinetic studies reveal that OleT_Sa is capable of decarboxylating elaidic acid, converting it to heptadeca-1,8-diene following addition of hydrogen peroxide, at the same rate and chemoselectivity as the conversion of stearic acid to 1-heptadecane. The X-ray crystal structure of the as purified OleT_Sa in complex with elaidic acid is also presented, allowing for several key residues to be identified for site-directed mutagenesis studies. The influence of the site-directed variants on C_18:0 and C_18:1 product formation, binding thermodynamics and kinetics have been investigated, showing that while spectral differences occur as a likely result of perturbing the binding pocket, this does not alter the chemoselectivity of the enzyme. Our work provides important insights into the mechanism of decarboxylation of an unsaturated fatty acid substrate by OleT_Sa potentially expanding the sustainable substrate space available for CYP152s.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"275 ","pages":"Article 113117"},"PeriodicalIF":3.2,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342434","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":"Oxidizable amino acids around cytochrome P450 hemes","authors":"Jay R. Winkler","doi":"10.1016/j.jinorgbio.2025.113119","DOIUrl":"10.1016/j.jinorgbio.2025.113119","url":null,"abstract":"<div><div>Cytochrome P450 enzymes (also designated with the prefix CYP) catalyze oxygenation reactions on a wide array of organic substrates. The reaction cycle involves two high-potential intermediates that are oxidized one and two electrons above the resting enzyme. We have suggested that hole transfer along chains of tryptophan, tyrosine, and cysteine residues can prevent enzyme damage by these intermediates when reaction with substrate fails. This work is an examination of the distributions of tryptophan, tyrosine, and cysteine residues closest to the heme in the structures of 188 P450 enzymes. Tyrosine residues tend to be closest in bacterial enzymes, whereas tryptophan residues dominate in eukaryotic enzymes. A tryptophan residue hydrogen-bonded to the D-propionate of the heme is a common structural motif in eukaryotes. A tryptophan in a similar location in the bacterial CYP102A1 enzyme has been shown in prior work to extend the lifetime of the enzyme during turnover. The eukaryotic tryptophan residues might perform a similar protective role.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"275 ","pages":"Article 113119"},"PeriodicalIF":3.2,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353404","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":"Examining Pseudohalide (N3, NCS, NCO) Coordination in Nonheme Fe(II) and Fe(III) Complexes","authors":"Vishal Yadav,&nbsp;Maxime A. Siegler,&nbsp;David P. Goldberg","doi":"10.1016/j.jinorgbio.2025.113107","DOIUrl":"10.1016/j.jinorgbio.2025.113107","url":null,"abstract":"<div><div>Pseudohalide ligands (N₃⁻, NCS⁻, NCO⁻) have emerged as valuable probes for studying nonheme iron halogenase reactivity due to their halogen-like behavior and distinct infrared (IR) spectroscopic signatures. Here, we present a systematic structural and vibrational analysis of a series of Fe(II) and Fe(III) complexes ligated by pseudohalides within a consistent tetradentate N₄O ligand framework (BNPA^Ph₂O⁻, BNPA^{Ph<em>(p-F)₂</em>}O⁻, and DPA^Ph₂O⁻). Single-crystal X-ray diffraction and IR spectroscopy reveal how variations in oxidation state, hydrogen bonding, trans ligands, and ligand electronics modulate Fe–X (X = N₃, NCS, NCO) bond lengths, angles, and stretching frequencies. While hydrogen bonding induces significant geometric distortions, it has minimal impact on azide vibrational energies. In contrast, subtle electronic modifications and trans ligand effects yield measurable shifts in vibrational frequencies, especially for NCS and NCO. Notably, axial versus equatorial ligand positioning leads to consistent vibrational splitting, enabling confident spectroscopic assignment of pseudohalide orientation. Oxidation state studies reveal a blue shift in ν(N₃) from Fe(II) to Fe(III), while NCS shows a red shift and NCO remains largely unaffected. These findings establish pseudohalides as vibrational reporters of coordination environment in nonheme iron systems and offer a foundation for their use in mechanistic studies of metalloenzymes and bioinspired catalysis.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"275 ","pages":"Article 113107"},"PeriodicalIF":3.2,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145463274","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":"Synthesis, structural characterization, in vitro and in vivo antitumor activities of Pt(II) complexes with di(pyridin-2-yl)methanone − hydrazone derivatives","authors":"Hai-Qun Zhang ,&nbsp;Nan-Feng Chen ,&nbsp;Hui-Chao Lin ,&nbsp;Muhammad Iqbal Choudhary ,&nbsp;Hong Liang ,&nbsp;Zhen-Feng Chen","doi":"10.1016/j.jinorgbio.2025.113114","DOIUrl":"10.1016/j.jinorgbio.2025.113114","url":null,"abstract":"<div><div>Six Pt(II) complexes bearing di(pyridin-2-yl)methanone hydrazone derivative ligands (<strong>Pt1 − Pt6</strong>) were synthesized and characterized. These complexes exhibited promising antiproliferative activity against multiple cancer cell lines, with low cytotoxicity toward normal human cells. Among them, <strong>Pt4</strong> and <strong>Pt6</strong> demonstrated the strongest inhibition of A2780 cell proliferation. Mechanistic studies revealed that <strong>Pt4</strong> and <strong>Pt6</strong> induce apoptosis <em>via</em> mitochondrial dysfunction, accumulation of intracellular Ca²⁺ and reactive oxygen species, and activation of caspase-3/9. Importantly, <strong>Pt4</strong>, the most potent agent against A2780 cells, displayed superior antitumor efficacy compared to cisplatin in an A2780 xenograft model, with no significant systemic toxicity.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"275 ","pages":"Article 113114"},"PeriodicalIF":3.2,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145317963","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 and CO metabolism by the canonical human heme oxygenases","authors":"Angela S. Fleischhacker ,&nbsp;Juan Blume-La-Torre ,&nbsp;Kierra Pendill ,&nbsp;Keion Dozier,&nbsp;Stephen W. Ragsdale","doi":"10.1016/j.jinorgbio.2025.113111","DOIUrl":"10.1016/j.jinorgbio.2025.113111","url":null,"abstract":"<div><div>Heme is an essential biomolecule and cofactor that participates in many different biological processes by binding to a diverse group of proteins to affect structure, function, and regulation. Yet, heme becomes toxic to human cells when its levels are elevated. As will be the focus of this review, the major route of heme detoxification in humans is through the heme degradation pathway involving heme oxygenase (HO). Humans, as well as other amniotes, express two isoforms of HO, HO1 and HO2, and understanding the role each isoform plays in regulating heme homeostasis is of great interest. Recently, a role for HO2 in sequestering, rather than degrading, heme has been uncovered. Here, we highlight this role of HO2 and place it in context of how, when, and why heme degradation proceeds, including the regulation of HO activity by the other necessary components of the reaction: oxygen and electrons from NAPDH via cytochrome P450 reductase. In addition, we review the significant roles the products of heme degradation (biliverdin, iron, and carbon monoxide) play in human health. Therefore, HO has many spheres of influence centered around substrates and products of the reaction, signifying the wide-reaching effects of heme degradation and sequestration.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"275 ","pages":"Article 113111"},"PeriodicalIF":3.2,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145323566","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 role of conserved elements in an active site α-helix of coproheme decarboxylase","authors":"Avery Carriuolo ,&nbsp;Shelby Parrott ,&nbsp;Olivia Bauer ,&nbsp;Clayton Pritchett ,&nbsp;Mika Baltes ,&nbsp;Robert S. Phillips ,&nbsp;William N. Lanzilotta","doi":"10.1016/j.jinorgbio.2025.113101","DOIUrl":"10.1016/j.jinorgbio.2025.113101","url":null,"abstract":"<div><div>The final step in the coproporphyrin-dependent (CPD) branch of the heme biosynthesis pathway involves the oxidative decarboxylation of coproheme to form heme b. This reaction, catalyzed by coproheme decarboxylase (ChdC), requires two equivalents of hydrogen peroxide to complete the synthesis of one b-type heme molecule. The CPD pathway is limited to Gram-positive bacteria and some archaea, and the precise mechanism of ChdC differs between Firmicutes and Actinobacteria. These variations highlight the importance of studying ChdCs from diverse organisms. The reaction proceeds through two sequential oxidative decarboxylations via the intermediate monovinyl monopropionate deuteroheme (MMD). Previous studies suggest that MMD does not exit the active site but instead undergoes a 90-degree rotation before another equivalent of hydrogen peroxide binds and initiates the second oxidative decarboxylation. This mechanism requires a high degree of specificity to distinguish between substrate, intermediate, and final product. To further understand this selectivity, we present biochemical and structural analyses of wild-type and variant forms of ChdC from <em>Streptomyces coelicolor</em> (<em>Sc</em>ChdC). We hypothesize that a conserved active site element within an alpha helix contributes to porphyrin specificity/selectivity and conformation and investigate how this influences an active site loop. Our data provides new insight into the role of this loop in substrate recognition, rotation, and catalysis. The substrate selectivity model for ChdC developed in this study will inform future mechanistic investigations and provide insights into key functional interfaces, highlighting potential targets for drug development.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"274 ","pages":"Article 113101"},"PeriodicalIF":3.2,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312045","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":"Metal ions control amyloid catalysis","authors":"Fiamma Ayelen Buratti ,&nbsp;Ranjeet Kumar ,&nbsp;Pernilla Wittung-Stafshede","doi":"10.1016/j.jinorgbio.2025.113112","DOIUrl":"10.1016/j.jinorgbio.2025.113112","url":null,"abstract":"<div><div>Pathological amyloids, such as those formed by the protein α-synuclein in Parkinson's disease, have recently been shown to catalyze hydrolysis of ester and phosphoester bonds in vitro. Here, we report that this activity is modulated by divalent metal ions copper (Cu(II)) and zinc (Zn(II)). Specifically, α-synuclein amyloids formed in the presence of Zn(II) are catalytically inactive towards dephosphorylation of adenosine triphosphate (ATP) and cannot bind a fluorescent analog of ATP. In contrast, amyloids formed in the presence of Cu(II) retain catalytic activity towards ATP that is comparable to that of amyloids formed without metal ions. Amyloids of the α-synuclein variant with histidine at position 50 replaced by alanine (H50A) are inactive in catalyzing ATP hydrolysis independent of Zn(II); however, when these amyloids are formed in the presence of Cu(II), catalytic activity and ATP binding is restored. For lipase activity on a model substrate, both wild-type and H50A α-synuclein amyloids are catalytically active regardless of Cu(II), whereas amyloids of both variants formed in the presence of Zn(II) exhibit no such activity. In sharp contrast, hydrolysis of para-nitrophenyl acetate (pNPA) is insensitive to both metal ions and H50A mutation in the amyloids. Given the common occurrence of metal ion dysregulation in neurodegenerative disorders, and the propensity of many amyloidogenic proteins to bind metal ions, our findings imply that amyloid catalytic activity may be modulated by metal ions in vivo.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"275 ","pages":"Article 113112"},"PeriodicalIF":3.2,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145317985","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}