Journal of Inorganic Biochemistry最新文献

{"title":"The oxygen sensitivity of [4Fe-4S] clusters on the nitrogenase scaffold protein NifU","authors":"Trevor D. Rapson ,&nbsp;Xueqin Wang ,&nbsp;Jessica K. Bilyj ,&nbsp;Christina M. Gregg ,&nbsp;Ingrid Venables ,&nbsp;Anu Mathew ,&nbsp;Julien Langley ,&nbsp;Nicholas Cox ,&nbsp;Guy N.L. Jameson ,&nbsp;Craig C. Wood","doi":"10.1016/j.jinorgbio.2026.113224","DOIUrl":"10.1016/j.jinorgbio.2026.113224","url":null,"abstract":"<div><div>The extreme oxygen sensitivity of nitrogenase enzymes poses a major obstacle to their use in biotechnology, particularly in engineering nitrogen-fixing plants. While the vulnerability of nitrogenase components NifH and NifDK to oxygen is well established, the sensitivity of the metal clusters on scaffold proteins involved in nitrogenase biosynthesis has not been previously reported. In this study, we investigate the oxygen sensitivity of the [4Fe-4S] clusters on the scaffold protein NifU, which supplies these clusters to several downstream targets, including NifH. Using UV/Vis, Mössbauer, and Electron Paramagnetic Resonance (EPR) spectroscopy, we show that exposure to oxygen converts the [4Fe-4S] clusters into [2Fe-2S] clusters. This degradation occurs rapidly, even at low oxygen levels (2 %). However, a fraction of the [4Fe-4S] clusters remain intact under these conditions, allowing NifU to activate apo-NifH by transferring functional clusters. In contrast, at atmospheric oxygen levels (21 %), all [4Fe-4S] clusters are damaged over 10 min, and NifU quickly loses its ability to reactivate apo-NifH.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113224"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964745","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":"Oxaliplatin-artesunate conjugate intensifies suppression on colorectal cancer by boosting antitumor immunity","authors":"Yehong Tan ,&nbsp;Tao Yang ,&nbsp;Siran Jiang ,&nbsp;Shumeng Li ,&nbsp;Linxiang Cai ,&nbsp;Ying Wang ,&nbsp;Zijian Guo ,&nbsp;Xiaoyong Wang","doi":"10.1016/j.jinorgbio.2026.113212","DOIUrl":"10.1016/j.jinorgbio.2026.113212","url":null,"abstract":"<div><div>Immunosuppressive tumor microenvironment is the major obstacle for antitumor immunotherapy. Elimination of myeloid-derived suppressor cells (MDSCs) potentiates immunotherapy for various solid tumors. Oxaliplatin-artesunate complex OPA decreases MDSCs by inhibiting CD33 and the triggering receptor expressed on myeloid cells 2 (TREM2) in the TME, and enhancing dendritic cell maturation due to its ability to facilitate immunogenic cell death and activate the cyclic-GMP-AMP synthase–stimulator of interferon genes (cGAS-STING) pathway. Moreover, OPA upregulates the costimulatory molecule CD28 and downregulates the immune checkpoint cytotoxic T lymphocyte-associated protein 4 (CTLA-4) on T cells, thus impeding the T cell depletion and immunosuppression. The activation of immune circulation and immunosignal pathway increases the chemotherapeutic activity of parent oxaliplatin. In addition, OPA serves as a cancer vaccine to inhibit tumor metastasis and reoccurrence. Lastly, the stability and safety profiles are superior to that of oxaliplatin. OPA is a unique chemoimmunotherapeutic agent with a distinct mechanism of action and prominent efficacy on orthotopic colorectal cancer in mouse models.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113212"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921913","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, and biological evaluation of a bioactive strontium (II)–mefenamic acid complex: In-vivo and in-silico insights","authors":"Ashraf Komal,&nbsp;Muhammad Azam,&nbsp;Bibi Saman,&nbsp;Riaz Maira,&nbsp;Muhammad Asim Raza Basra","doi":"10.1016/j.jinorgbio.2025.113196","DOIUrl":"10.1016/j.jinorgbio.2025.113196","url":null,"abstract":"<div><div>Metal-based coordination complexes of existing drugs, a step towards to natural system, are gaining the attention of scientists due to their boosted pharmaceutical outcomes with minimal side effect on health. The new mononuclear strontium (Sr) complex of mefenamic acid (Mef) and triethylamine (TEA), [Sr(mef)₂(TEA)₂].4H₂O was manufactured and characterized by using Elemental analysis, UV-VIS spectra, FTIR, SEM-EDX,¹H and ¹³C NMR, TGA, and PXRD. Its free radical scavenging and metal chelating potential of the synthesized compound was assessed by five different <em>in vitro</em> antioxidant assays, while <em>in vivo</em> activities evaluated the anti-inflammatory, analgesic and anxiolytic activities. The studied complex contained Sr(II) metal, which is coordinated to two mefenamato ligands through one oxygen atom of each and two TEA through their nitrogen atoms. In the studied complex, Mef acts as monodentate ligand, and TEA serves as auxiliary ligand. The complex exhibited potent antioxidant activities especially lowest IC₅₀ = 5.6 μM for iron-reducing assay, significant anti-inflammatory response (<em>P</em> &lt; 0.001), and strong analgesic effect (<em>P</em> &lt; 0.0001) compared to the free ligand. <em>In-silico</em> ADMET study showed safe drug profiling for Sr-complex than only ligand and biological prediction of biological activities by PASS online webserver further confirmed the better bioactivities ((Pa &gt; Pi) of pharmacological relevance. With further molecular insight, the synthesized complex may serve as promising lead compound for anti-inflammatory drug development.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113196"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145802188","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":"Lewis acid-promoted self-sensitized photocatalytic CO2 reduction by a bimetallic Fe complex","authors":"Matthias Huber,&nbsp;Corinna R. Hess","doi":"10.1016/j.jinorgbio.2026.113230","DOIUrl":"10.1016/j.jinorgbio.2026.113230","url":null,"abstract":"<div><div>The modified macrocyclic Mabiq ligand, ^{<strong>MeO</strong>}<strong>Mbq</strong>, contains two methoxy groups at the outer biquinazoline unit that allow for coordination of a second metal ion in the absence of auxiliary ligands. A series of bimetallic <strong>MFe</strong>^{<strong>MeO</strong>}<strong>Mbq</strong> complexes was synthesized, containing Na, Mg, Fe or Zn adjacent to a centrally bound ferrous ion. The redox properties correlate with the Lewis acidity of the supporting metal. Both Fe and Zn in the outer site boost the photocatalytic CO₂ reduction activity of the central ferrous site. The bimetallic <strong>ZnFe</strong>^{<strong>MeO</strong>}<strong>Mbq</strong> achieves up to 140 TONs (1 h) for selective CO₂ to CO conversion in a self-sensitized process.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113230"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023367","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 and lanthanum coordination of a BzMacropa analogue for convenient solid-phase peptide synthesis towards targeted alpha therapeutic discovery","authors":"Nicholas A. Bainbridge ,&nbsp;Leonard G. Luyt","doi":"10.1016/j.jinorgbio.2025.113189","DOIUrl":"10.1016/j.jinorgbio.2025.113189","url":null,"abstract":"<div><div>The alpha-emitting isotope actinium-225 is a promising radiometal for developing targeted alpha therapeutics (TAT) to treat malignant diseases. Actinium-225 has a half-life of 9.92 days and a decay chain emitting four alpha-particles. Alpha particle therapeutics are particularly attractive for their precise treatment while sparing surrounding tissue. Effective application of actinium-225 in radiopharmaceutical design requires a chelator that stably coordinates the metal and enables bioconjugation to targeting vectors. BzMacropa, a benzyl-fused diaza-18-crown-6 macrocyclic ligand, exhibits favorable binding properties but is incompatible with peptide-based radiopharmaceuticals synthesized using solid-phase peptide synthesis (SPPS) due to undesirable side reactions such as dimerization, offering limited conjugation flexibility. We report a synthetic route to a protected analogue of BzMacropa integrated with protected tert-butyl ester picolinic acid pendant arms with a free carboxylic acid handle enabling flexible conjugation strategies. The protected chelator was successfully synthesized at the multigram scale and was coupled to the C-X-C chemokine type 4 (CXCR4)-targeting peptide FC122 under SPPS conditions. The resulting conjugate was complexed with lanthanum (III), a non-radioactive surrogate for actinium-225. This work demonstrates a high-yielding, scalable synthesis and a modular platform for developing BzMacropa-peptide conjugates, providing an effective approach to the synthesis of next-generation peptide-based TAT radiopharmaceuticals.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113189"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145832084","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":"Copper-polypyridine complexes as potent SARS-CoV-2 3CLpro inhibitors: Synthesis, evaluation, and molecular basis based on computational study","authors":"Xiaolin Jiang ,&nbsp;Haoyu Zhang ,&nbsp;Shiyu Ping ,&nbsp;Yaru Zou ,&nbsp;Liguang Zhang","doi":"10.1016/j.jinorgbio.2026.113214","DOIUrl":"10.1016/j.jinorgbio.2026.113214","url":null,"abstract":"<div><div>The COVID-19 pandemic, driven by SARS-CoV-2, has underscored the urgent need for effective antiviral agents. Research targeting the main protease (3CL^pro), a crucial enzyme in the viral replication process, offers a promising strategy for antiviral drug development. Metals are not only fundamental to the human body but also central to the field of inorganic biochemistry. In this study, we report the design and synthesis of a novel polypyridyl di‑copper coordination complex with superior structural stability and antiviral activity, and characterized by various analytical and spectral techniques. Among the tested compounds, the tetrapyridine‑copper complex (<strong>B2</strong>) featuring a nitrate counterion demonstrated exceptional inhibition of 3CL^pro and tolerable cytotoxicity. The strong Cu<img>Cu synergy enables it to adopt a more compact conformation and establish favorable interactions with 3CL^pro. These attributes position it as a compelling candidate for future antiviral therapeutics. Additionally, molecular docking, molecular dynamics simulations, and free energy calculations were employed to elucidate the binding interactions and identify key residues for inhibitor optimization.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113214"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921995","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":"Editorial: Special issue on iron-sulfur proteins","authors":"Patricia C. Dos Santos ,&nbsp;Jeffrey M. Boyd","doi":"10.1016/j.jinorgbio.2026.113238","DOIUrl":"10.1016/j.jinorgbio.2026.113238","url":null,"abstract":"","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113238"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146091677","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":"Iridium(III) and rhenium(I) complexes containing an IDO inhibitor induce apoptosis and pyroptosis","authors":"Hou Zhu ,&nbsp;Yong-Sheng Yang ,&nbsp;Lin-Yuan Zhu,&nbsp;Chun-Rong Jiang,&nbsp;Zheng Zhang,&nbsp;Meng-Ting Xu,&nbsp;Rong-Tao Li,&nbsp;Rui-Rong Ye","doi":"10.1016/j.jinorgbio.2026.113216","DOIUrl":"10.1016/j.jinorgbio.2026.113216","url":null,"abstract":"<div><div>Four novel Ir(III)/Re(I)-1-methyl-D-tryptophan conjugates (<strong>Ir-MT-1</strong>–<strong>2</strong> and <strong>Re-MT-1</strong>–<strong>2</strong>) were designed and synthesized for the first time, among which 1-methyl-D-tryptophan (1-MT) is an indoleamine 2,3-dioxygenase (IDO) inhibitor. Three (<strong>Ir-MT-1</strong>–<strong>2</strong> and <strong>Re-MT-1</strong>) of the metal-conjugates showed high-efficient anti-tumor activities against human cervical cancer HeLa cells, with IC₅₀ values of 5.2, 7.1, and 4.4 μM, respectively, and significantly inhibited IDO expression. Mechanistic investigations revealed that these complexes selectively localized to mitochondria, inducing mitochondrial membrane potential (MMP) depolarization, elevating intracellular reactive oxygen species (ROS) levels, activating mitochondrial apoptotic pathways, and simultaneously inducing the cleavage of pyroptosis marker (GSDME) to cause pyroptosis. These results demonstrate the potential of combing transition metals with IDO inhibitors for cancer treatment.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113216"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921998","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":"Spectroscopic characterization of Mn2+-induced catalysis in cyclic GMP-AMP synthase","authors":"Karis Williamson,&nbsp;Karina Sharafutdinova,&nbsp;Micah Gaddy,&nbsp;Lucy Jolley,&nbsp;Parker Tamucci,&nbsp;Jaren Lobb,&nbsp;Eleana Parks,&nbsp;Noah Griffin,&nbsp;Molly M. Lockart","doi":"10.1016/j.jinorgbio.2025.113200","DOIUrl":"10.1016/j.jinorgbio.2025.113200","url":null,"abstract":"<div><div>Cyclic GMP-AMP synthase (cGAS) is a nucleotidyltransferase enzyme that functions as the principal cytosolic sensor of double-stranded DNA (dsDNA) in vertebrates. Upon binding dsDNA, cGAS produces the second messenger 2′3′-cyclic GMP-AMP (2′3′-cGAMP), initiating innate immune signaling. Canonical models describe activation through dsDNA-induced dimerization and recruitment of two Mg²⁺ ions into the active site. Recent studies, however, have identified Mn²⁺ as an alternative cofactor that accelerates catalysis, enhances substrate selectivity, and improves product fidelity. Interestingly, in the presence of dsDNA, Mn²⁺ acts as the preferred catalytic metal, and in its absence, it can promote dsDNA-independent synthesis of 2′3′-cGAMP. The metal-dependent divergence in activity raises key questions about the composition of the active metal cluster and the molecular basis for catalytic enhancement. Here, liquid chromatography–tandem mass spectrometry (LC-MS/MS) and electron paramagnetic resonance (EPR) spectroscopy, including electron spin echo envelope modulation (ESEEM) and electron–nuclear double resonance (ENDOR), were used to probe Mn²⁺ coordination and its interaction with substrates. Mn²⁺–cGAS generated approximately sixfold more cGAMP than Mg²⁺–cGAS with dsDNA and fourteenfold more without dsDNA, confirming enhanced catalysis and dsDNA-independent activation. CW and pulsed EPR revealed that Mn²⁺ uptake occurs during active-site assembly and that Mn²⁺ is coordinated by ATP and protein-derived ligands in the substrate-bound complex. These results provide the first spectroscopic description of Mn²⁺ coordination in cGAS and offer critical mechanistic insight into its metal-dependent activation and broader role in health and disease. Additionally, this work further defines how metal cofactors regulate innate immune signaling by cGAS.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113200"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145802165","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":"Structural and mechanistic insights into the sulfur transfer protein SufU from Staphylococcus aureus","authors":"Emily Sabo ,&nbsp;Connor Nelson ,&nbsp;Delanie Huntoon ,&nbsp;Jing Yang ,&nbsp;Martin Kirk ,&nbsp;Simon J. George ,&nbsp;Brian Bennett ,&nbsp;Jeffrey M. Boyd ,&nbsp;Richard C. Holz","doi":"10.1016/j.jinorgbio.2025.113205","DOIUrl":"10.1016/j.jinorgbio.2025.113205","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Substitution of the active site Zn&lt;sup&gt;2+&lt;/sup&gt; ion in the sulfur transfer protein (SufU) from &lt;em&gt;Staphylococcus aureus&lt;/em&gt; (&lt;em&gt;Sa&lt;/em&gt;SufU) with a catalytically active Co&lt;sup&gt;2+&lt;/sup&gt; ion revealed a S&lt;sup&gt;−&lt;/sup&gt;➔Co&lt;sup&gt;2+&lt;/sup&gt; ligand-to-metal-charge-transfer (LMCT) band at 340 nm with an &lt;em&gt;ε&lt;/em&gt; of &lt;em&gt;∼&lt;/em&gt;&lt;span&gt;&lt;math&gt;&lt;mn&gt;2,760&lt;/mn&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;msup&gt;&lt;mi&gt;M&lt;/mi&gt;&lt;mrow&gt;&lt;mo&gt;−&lt;/mo&gt;&lt;mn&gt;1&lt;/mn&gt;&lt;/mrow&gt;&lt;/msup&gt;&lt;msup&gt;&lt;mi&gt;cm&lt;/mi&gt;&lt;mrow&gt;&lt;mo&gt;−&lt;/mo&gt;&lt;mn&gt;1&lt;/mn&gt;&lt;/mrow&gt;&lt;/msup&gt;&lt;/math&gt;&lt;/span&gt;, as well as &lt;em&gt;d-d&lt;/em&gt; (i.e. ligand field) absorption bands at 584 nm (&lt;em&gt;ε&lt;/em&gt; = 540 &lt;span&gt;&lt;math&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;msup&gt;&lt;mi&gt;M&lt;/mi&gt;&lt;mrow&gt;&lt;mo&gt;−&lt;/mo&gt;&lt;mn&gt;1&lt;/mn&gt;&lt;/mrow&gt;&lt;/msup&gt;&lt;msup&gt;&lt;mi&gt;cm&lt;/mi&gt;&lt;mrow&gt;&lt;mo&gt;−&lt;/mo&gt;&lt;mn&gt;1&lt;/mn&gt;&lt;/mrow&gt;&lt;/msup&gt;&lt;/math&gt;&lt;/span&gt;), 636 nm (&lt;em&gt;ε&lt;/em&gt; = 580 &lt;span&gt;&lt;math&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;msup&gt;&lt;mi&gt;M&lt;/mi&gt;&lt;mrow&gt;&lt;mo&gt;−&lt;/mo&gt;&lt;mn&gt;1&lt;/mn&gt;&lt;/mrow&gt;&lt;/msup&gt;&lt;msup&gt;&lt;mi&gt;cm&lt;/mi&gt;&lt;mrow&gt;&lt;mo&gt;−&lt;/mo&gt;&lt;mn&gt;1&lt;/mn&gt;&lt;/mrow&gt;&lt;/msup&gt;&lt;/math&gt;&lt;/span&gt;) and 735 nm (&lt;em&gt;ε&lt;/em&gt; = 220 &lt;span&gt;&lt;math&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;msup&gt;&lt;mi&gt;M&lt;/mi&gt;&lt;mrow&gt;&lt;mo&gt;−&lt;/mo&gt;&lt;mn&gt;1&lt;/mn&gt;&lt;/mrow&gt;&lt;/msup&gt;&lt;msup&gt;&lt;mi&gt;cm&lt;/mi&gt;&lt;mrow&gt;&lt;mo&gt;−&lt;/mo&gt;&lt;mn&gt;1&lt;/mn&gt;&lt;/mrow&gt;&lt;/msup&gt;&lt;/math&gt;&lt;/span&gt;). These data suggest a distorted four- or five-coordinate Co&lt;sup&gt;2+&lt;/sup&gt; center ligated by 3 Cys residues with a dissociation constant (&lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mi&gt;K&lt;/mi&gt;&lt;mi&gt;d&lt;/mi&gt;&lt;/msub&gt;&lt;mo&gt;)&lt;/mo&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;/math&gt;&lt;/span&gt;of ∼&lt;span&gt;&lt;math&gt;&lt;mn&gt;600&lt;/mn&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mi&gt;n&lt;/mi&gt;&lt;/math&gt;&lt;/span&gt;M. Co K-edge absorption spectra (XAS) of Co&lt;sup&gt;2+&lt;/sup&gt;-&lt;em&gt;Sa&lt;/em&gt;SufU indicated five-coordinate Co&lt;sup&gt;2+&lt;/sup&gt;, while extended X-ray absorption fine structure (EXAFS) spectra of Co&lt;sup&gt;2+&lt;/sup&gt;-&lt;em&gt;Sa&lt;/em&gt;SufU revealed 2 N/O and 3 S ligands. EXAFS data for Zn&lt;sup&gt;2+&lt;/sup&gt;-&lt;em&gt;Sa&lt;/em&gt;SufU revealed 1 N/O and 3 S ligands consistent with the proposed Cys&lt;sub&gt;3&lt;/sub&gt;Asp coordinating residues. The fifth ligand in the Co&lt;sup&gt;2+&lt;/sup&gt;-SaSufU enzyme is either a bidentate the active site Asp ligand or an exogenous water. Upon the addition of &lt;em&gt;Sa&lt;/em&gt;SufS to either Zn&lt;sup&gt;2+&lt;/sup&gt;-&lt;em&gt;Sa&lt;/em&gt;SufU or Co&lt;sup&gt;2+&lt;/sup&gt;-&lt;em&gt;Sa&lt;/em&gt;SufU, XAS and EXAFS data suggest that one of the S ligands is displaced by an N/O atom donor. Interestingly, electronic absorption data suggest that this only occurs in the presence of Cys. EPR analysis of Co&lt;sup&gt;2+&lt;/sup&gt;&lt;em&gt;-Sa&lt;/em&gt;SufU revealed temperature- and &lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mi&gt;B&lt;/mi&gt;&lt;mn&gt;1&lt;/mn&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt;-dependent transitions within both the &lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mi&gt;M&lt;/mi&gt;&lt;mi&gt;s&lt;/mi&gt;&lt;/msub&gt;&lt;mo&gt;=&lt;/mo&gt;&lt;mo&gt;±&lt;/mo&gt;&lt;mfrac&gt;&lt;mn&gt;1&lt;/mn&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/mfrac&gt;&lt;/math&gt;&lt;/span&gt; and &lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mi&gt;M&lt;/mi&gt;&lt;mi&gt;S&lt;/mi&gt;&lt;/msub&gt;&lt;mo&gt;=&lt;/mo&gt;&lt;mo&gt;±&lt;/mo&gt;&lt;mfrac&gt;&lt;mn&gt;3&lt;/mn&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/mfrac&gt;&lt;/math&gt;&lt;/span&gt; doublets of the &lt;span&gt;&lt;math&gt;&lt;mi&gt;S&lt;/mi&gt;&lt;mo&gt;=&lt;/mo&gt;&lt;mfrac&gt;&lt;mn&gt;3&lt;/mn&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/mfrac&gt;&lt;/math&gt;&lt;/span&gt; spin system that suggested either heterogeneity of the electronic structure or an unusually small zero-field splitting for Co(II). Taken together, these data provide in-solution evidence for the mechanism of S&lt;sup&gt;2−&lt;/sup&gt; transfer from &lt;em&gt;Sa&lt;/em&gt;SufS to &lt;em&gt;Sa&lt;/em","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113205"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145861648","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}