Journal of Biological Inorganic Chemistry最新文献

{"title":"Organoselenium transition metal complexes as promising candidates in medicine area","authors":"Marina Kostić,&nbsp;Jovana Marjanović,&nbsp;Vera Divac","doi":"10.1007/s00775-024-02072-y","DOIUrl":"10.1007/s00775-024-02072-y","url":null,"abstract":"<div><p>The medicinal properties of transition metal complexes are greatly influenced by the nature and physico-chemical features of the ligand present in the complex structure. Due to the unique biological properties of the organoselenium compounds reflected in the variety of pharmacological activities (such as antioxidative, antiviral, antimicrobial and anticancer), the last years have brought increased interest for their use as a ligands compounds in the design and syntheses of range of transition metal-based coordination compounds that have been explored as antitumor and antimicrobial agents. Our aim in this review is to provide the overview of an recent development of the transition metal complexes bearing organoselenium ligands in the structure that could be promising choice for the treatment of various diseases, particularly cancer and infective diseases. For this purpose, the complexes of Co, Ni, Cu, Zn, Ru, Pd, Pt, Au and Sn as the most explored examples will be included and discussed.</p></div>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":"29 6","pages":"555 - 571"},"PeriodicalIF":2.7,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911276","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":"Selective removal of copper from complex biological media with an agarose-immobilized high-affinity PSP ligand","authors":"Arielle Nabatilan,&nbsp;M. Thomas Morgan,&nbsp;Sara Netzer,&nbsp;Christoph J. Fahrni","doi":"10.1007/s00775-024-02065-x","DOIUrl":"10.1007/s00775-024-02065-x","url":null,"abstract":"<div><p>The elucidation of metal-dependent biological processes requires selective reagents for manipulating metal ion levels within biological solutions such as growth media or cell lysates. To this end, we immobilized a phosphine sulfide-stabilized phosphine (PSP) ligand on agarose to create a resin for the selective removal of copper from chemically complex biological media through simple filtration or centrifugation. Comprised of a conformationally preorganized phenylene-bridged backbone, the PSP-ligand binds Cu(I) with a 1:1 stoichiometry and exhibits a pH-independent Cu(I) dissociation constant in the low zeptomolar range. Neither Zn(II), Fe(II), nor Mn(II) interact with the ligand at millimolar concentrations, thus offering a much-improved selectivity towards copper over other commonly employed solid-supported chelators such as Chelex 100. As revealed by X-ray fluorescence elemental analysis, the immobilized chelator effectively removes copper from cell culture growth media and cell lysate isolated from mouse fibroblasts. In addition to preparing copper-depleted media or cell lysates for biological studies, PSP-immobilized ligands might prove equally useful for applications in radiochemistry, materials science, and environmental science.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":"29 5","pages":"531 - 540"},"PeriodicalIF":2.7,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141776588","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":"Indium(III) complexes with lapachol: cytotoxic effects against human breast tumor cells and interactions with DNA","authors":"Alexandre B. de Carvalho,&nbsp;Ana M. S. Souza,&nbsp;Larissa Pereira Bento,&nbsp;Mariana de Oliveira Silva,&nbsp;Elaine M. Souza-Fagundes,&nbsp;Renata Diniz,&nbsp;Heloisa Beraldo","doi":"10.1007/s00775-024-02062-0","DOIUrl":"10.1007/s00775-024-02062-0","url":null,"abstract":"<div><p>Lapachol (2-hydroxy-3-(3-methylbut-2-en-1-yl)naphthalene-1,4-dione) is a 1,4-naphthoquinone-derived natural product that presents numerous bioactivities and was shown to have cytotoxic effects against several human tumor cells. Indium(III) complexes with a variety of ligands also exhibit antineoplastic activity. Indium(III) complexes [In(lap)Cl₂].4H₂O (<b>1</b>), [In(lap)₂Cl(Et₃N)] (<b>2</b>), [In(lap)₃]·2H₂O (<b>3</b>) [In(lap)(bipy)Cl₂] bipy = 2,2′-bipyridine (<b>4</b>) and [In(lap)(phen)Cl₂] phen = 1,10-phenanthroline (<b>5</b>) were obtained with 2-hydroxy-3-(3-methylbut-2-en-1-yl)naphthalene-1,4-dione (lapachol). Crystal structure determinations for (<b>4</b>) and (<b>5</b>) revealed that the indium(III) center is coordinated to two O atoms from lapachol, two N atoms from 1,10-phenanthroline or 2,2′-bipyridine, and two chloride anions, in a distorted octahedral geometry. Although both complexes (<b>4</b>) and (<b>5</b>) interacted with CT-DNA in vitro by an intercalative mode, only <b>5</b> exhibited cytotoxicity against MCF-7 and MDA-MB breast tumor cells. 1,10-phenanthroline and complex (<b>5</b>) presented cytotoxic effects against MCF-7 and MDA-MB cells, with complex (<b>5</b>) being threefold more active than 1,10-phenanthroline on MCF-7 cells. In addition, complex (<b>5</b>) significantly reduced the formation of MDA-MB-231 colonies in a clonogenicity assay. The foregoing results suggest that further studies on the cytotoxic effects and cellular targets of complex (<b>5</b>) are of utmost relevance.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":"29 5","pages":"519 - 529"},"PeriodicalIF":2.7,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618933","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":"Nanoarchitectonics for synergistic activity of multimetallic nanohybrids as a possible approach for antimicrobial resistance (AMR)","authors":"Piumika N. Yapa,&nbsp;Imalka Munaweera,&nbsp;Manjula M. Weerasekera,&nbsp;Laksiri Weerasinghe","doi":"10.1007/s00775-024-02066-w","DOIUrl":"10.1007/s00775-024-02066-w","url":null,"abstract":"<div><p>The global threat posed by antimicrobial resistance (AMR) to public health is an immensurable problem. The effectiveness of treating infections would be more at risk in the absence of effective antimicrobials. Researchers have shown an amplified interest in alternatives, such as developing advanced metallic nanohybrids as new therapeutic candidates for antibiotics due to their promising effectiveness against resistant microorganisms. In recent decades, the antimicrobial activity of monometallic nanoparticles has received extensive study and solid proof, providing new opportunities for developing multimetallic nanohybrid antimicrobials. Advanced metallic nanohybrids are an emerging remedy for a number of issues that develop in the field of medicine. Advanced metallic nanohybrids have shown a promising ability to combat resistant microorganisms due to their overall synergistic activity. Formulating advanced multimetallic nanohybrids falling under the umbrella of the growing field of nanoarchitectonics, which extends beyond nanotechnology. The underlying theory of nanoarchitectonics involves utilizing nanoscale units that follow the concepts of nanotechnology to architect nanomaterials. This review focuses on a comprehensive description of antimicrobial mechanisms of metallic nanohybrids and their enabling future insights on the research directions of developing the nanoarchitectonics of advanced multimetallic nanohybrids as novel antibiotics through their synergistic activity.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"29 5","pages":"477 - 498"},"PeriodicalIF":2.7,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589336","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":"An organometallic hybrid antibiotic of metronidazole with a Gold(I) N-Heterocyclic Carbene overcomes metronidazole resistance in Clostridioides difficile","authors":"Rolf Büssing,&nbsp;Arne Bublitz,&nbsp;Bianka Karge,&nbsp;Mark Brönstrup,&nbsp;Till Strowig,&nbsp;Ingo Ott","doi":"10.1007/s00775-024-02064-y","DOIUrl":"10.1007/s00775-024-02064-y","url":null,"abstract":"<div><p>Antimicrobial resistance (AMR) has been emerging as a major global health threat and calls for the development of novel drug candidates. Metal complexes have been demonstrating high efficiency as antibacterial agents that differ substantially from the established types of antibiotics in their chemical structures and their mechanism of action. One strategy to exploit this potential is the design of metal-based hybrid organometallics that consist of an established antibiotic and a metal-based warhead that contributes an additional mechanism of action different from that of the parent antibiotic. In this communication, we describe the organometallic hybrid antibiotic <b>2c</b>, in which the drug metronidazole is connected to a gold(I) N-heterocyclic carbene warhead that inhibits bacterial thioredoxin reductase (TrxR). Metronidazole can be used for the treatment with the obligatory anaerobic pathogen <i>Clostridioides difficile</i> (<i>C. difficile</i>), however, resistance to the drug hampers its clinical success. The gold organometallic conjugate <b>2c</b> was an efficient inhibitor of TrxR and it was inactive or showed only minor effects against eucaryotic cells and bacteria grown under aerobic conditions. In contrast, a strong antibacterial effect was observed against both metronidazole-sensitive and -resistant strains of <i>C. difficile</i>. This report presents a proof-of-concept that the design of metal-based hybrid antibiotics can be a viable approach to efficiently tackle AMR.</p><h3>Graphical abstract</h3><p>A metronidazole-gold hybrid metalloantibiotic with high efficacy against resistant C. difficile </p><div><figure><div><div><picture><img></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"29 5","pages":"511 - 518"},"PeriodicalIF":2.7,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11343806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454502","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":"The first evaluation of the in vitro effects of silver(I)-N-heterocyclic carbene complexes on Encephalitozoon intestinalis and Leishmania major promastigotes","authors":"Ahmet Duran Ataş,&nbsp;Zübeyda Akın-Polat,&nbsp;Derya Gül Gülpınar,&nbsp;Neslihan Şahin","doi":"10.1007/s00775-024-02063-z","DOIUrl":"10.1007/s00775-024-02063-z","url":null,"abstract":"<div><p><i>Encephalitozoon intestinalis</i> is an opportunistic microsporidian parasite that primarily infects immunocompromised individuals, such as those with HIV/AIDS or undergoing organ transplantation. Leishmaniasis is responsible for parasitic infections, particularly in developing countries. The disease has not been effectively controlled due to the lack of an effective vaccine and affordable treatment options. Current treatment options for <i>E. intestinalis</i> infection and leishmaniasis are limited and often associated with adverse side effects. There is no previous study in the literature on the antimicrosporidial activities of Ag(I)-<i>N</i>-heterocyclic carbene compounds. In this study, the in vitro antimicrosporidial activities of previously synthesized Ag(I)-<i>N</i>-heterocyclic carbene complexes were evaluated using <i>E. intestinalis</i> spores cultured in human renal epithelial cell lines (HEK-293). Inhibition of microsporidian replication was determined by spore counting. In addition, the effects of the compounds on <i>Leishmania major</i> promastigotes were assessed by measuring metabolic activity or cell viability using a tetrazolium reaction. Statistical analysis was performed to determine significant differences between treated and control groups. Our results showed that the growth of <i>E. intestinalis</i> and <i>L. major</i> promastigotes was inhibited by the tested compounds in a concentration-dependent manner. A significant decrease in parasite viability was observed at the highest concentrations. These results suggest that the compounds have potential anti-microsporidial and anti-leishmanial activity. Further research is required to elucidate the underlying mechanisms of action and to evaluate the efficacy of the compounds in animal models or clinical trials.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"29 5","pages":"499 - 509"},"PeriodicalIF":2.7,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11343777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141449248","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":"An N-terminal acidic β-sheet domain is responsible for the metal-accumulation properties of amyloid-β protofibrils: a molecular dynamics study","authors":"Carlos Z. Gómez-Castro,&nbsp;Liliana Quintanar,&nbsp;Alberto Vela","doi":"10.1007/s00775-024-02061-1","DOIUrl":"10.1007/s00775-024-02061-1","url":null,"abstract":"<div><p>The influence of metal ions on the structure of amyloid-<span>(beta )</span> (Aβ) protofibril models was studied through molecular dynamics to explore the molecular mechanisms underlying metal-induced Aβ aggregation relevant in Alzheimer’s disease (AD). The models included 36-, 48-, and 188-mers of the Aβ₄₂ sequence and two disease-modifying variants. Primary structural effects were observed at the N-terminal domain, as it became susceptible to the presence of cations. Specially when β-sheets predominate, this motif orients N-terminal acidic residues toward one single face of the β-sheet, resulting in the formation of an acidic region that attracts cations from the media and promotes the folding of the N-terminal region, with implications in amyloid aggregation. The molecular phenotype of the protofibril models based on Aβ variants shows that the AD-causative D7N mutation promotes the formation of N-terminal β-sheets and accumulates more Zn²⁺, in contrast to the non-amyloidogenic rodent sequence that hinders the β-sheets and is more selective for Na⁺ over Zn²⁺ cations. It is proposed that forming an acidic β-sheet domain and accumulating cations is a plausible molecular mechanism connecting the elevated affinity and concentration of metals in Aβ fibrils to their high content of β-sheet structure at the N-terminal sequence.</p><h3>Graphic abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"29 4","pages":"407 - 425"},"PeriodicalIF":2.7,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174002","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":"Catalytic role of histidine-114 in the hydrolytic dehalogenation of chlorothalonil by Pseudomonas sp. CTN-3","authors":"Grayson Gerlich,&nbsp;Callie Miller,&nbsp;Xinhang Yang,&nbsp;Karla Diviesti,&nbsp;Brian Bennett,&nbsp;Judith Klein-Seetharaman,&nbsp;Richard C. Holz","doi":"10.1007/s00775-024-02053-1","DOIUrl":"10.1007/s00775-024-02053-1","url":null,"abstract":"<div><p>Chlorothalonil (2,4,5,6-tetrachloroisophthalonitrile; TPN) is an environmentally persistent fungicide that sees heavy use in the USA and is highly toxic to aquatic species and birds, as well as a probable human carcinogen. The chlorothalonil dehalogenase from <i>Pseudomonas</i> sp. CTN-3 (Chd, UniProtKB C9EBR5) degrades TPN to its less toxic 4-OH-TPN analog making it an exciting candidate for the development of a bioremediation process for TPN; however, little is currently known about its catalytic mechanism. Therefore, an active site residue histidine-114 (His114) which forms a hydrogen bond with the Zn(II)-bound water/hydroxide and has been suggested to be the active site acid/base, was substituted by an Ala residue. Surprisingly, Chd^H114A exhibited catalytic activity with a <i>k</i>_<i>cat</i> value of 1.07 s⁻¹, ~ 5% of wild-type (WT) Chd, and a <i>K</i>_<i>M</i> of 32 µM. Thus, His114 is catalytically important but not essential. The electronic and structural aspects of the WT Chd and Chd^H114A active sites were examined using UV–Vis and EPR spectroscopy on the catalytically competent Co(II)-substituted enzyme as well as all-atomistic molecular dynamics (MD) simulations. Combination of these data suggest His114 can quickly and reversibly move nearly 2 Å between one conformation that facilitates catalysis and another that enables product egress and active site recharge. In light of experimental and computational data on Chd^H114A, Asn216 appears to play a role in substrate binding and preorganization of the transition-state while Asp116 likely facilitates the deprotonation of the Zn(II)-bound water in the absence of His114. Based on these data, an updated proposed catalytic mechanism for Chd is presented.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"29 4","pages":"427 - 439"},"PeriodicalIF":2.7,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141152117","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":"Iron mobilization from intact ferritin: effect of differential redox activity of quinone derivatives with NADH/O2 and in situ-generated ROS","authors":"Narmada Behera,&nbsp;Gargee Bhattacharyya,&nbsp;Satyabrat Behera,&nbsp;Rabindra K. Behera","doi":"10.1007/s00775-024-02058-w","DOIUrl":"10.1007/s00775-024-02058-w","url":null,"abstract":"<div><p>Ferritins are multimeric nanocage proteins that sequester/concentrate excess of free iron and catalytically synthesize a hydrated ferric oxyhydroxide bio-mineral. Besides functioning as the primary intracellular iron storehouses, these supramolecular assemblies also oversee the controlled release of iron to meet physiologic demands. By virtue of the reducing nature of the cytosol, reductive dissolution of ferritin-iron bio-mineral by physiologic reducing agents might be a probable pathway operating in vivo. Herein, to explore this reductive iron-release pathway, a series of quinone analogs differing in size, position/nature of substituents and redox potentials were employed to relay electrons from physiologic reducing agent, NADH, to the ferritin core. Quinones are well known natural electron/proton mediators capable of facilitating both 1/2 electron transfer processes and have been implicated in iron/nutrient acquisition in plants and energy transduction. Our findings on the structure–reactivity of quinone mediators highlight that iron release from ferritin is dictated by electron-relay capability (dependent on E_1/2 values) of quinones, their molecular structure (i.e., the presence of iron-chelation sites and the propensity for H-bonding) and the type/amount of reactive oxygen species (ROS) they generate in situ. Juglone/Plumbagin released maximum iron due to their intermediate E_1/2 values, presence of iron chelation sites, the ability to inhibit in situ generation of H₂O₂ and form intramolecular H-bonding (possibly promotes semiquinone formation). This study may strengthen our understanding of the ferritin-iron-release process and their significance in bioenergetics/O₂-based cellular metabolism/toxicity while providing insights on microbial/plant iron acquisition and the dynamic host–pathogen interactions.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"29 4","pages":"455 - 475"},"PeriodicalIF":2.7,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080148","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":"The critical role of a conserved lysine residue in periplasmic nitrate reductase catalyzed reactions","authors":"Nitai C. Giri,&nbsp;Breeanna Mintmier,&nbsp;Manohar Radhakrishnan,&nbsp;Jonathan W. Mielke,&nbsp;Jarett Wilcoxen,&nbsp;Partha Basu","doi":"10.1007/s00775-024-02057-x","DOIUrl":"10.1007/s00775-024-02057-x","url":null,"abstract":"<div><p>Periplasmic nitrate reductase NapA from <i>Campylobacter jejuni</i> (<i>C. jejuni</i>) contains a molybdenum cofactor (Moco) and a 4Fe–4S cluster and catalyzes the reduction of nitrate to nitrite. The reducing equivalent required for the catalysis is transferred from NapC → NapB → NapA. The electron transfer from NapB to NapA occurs through the 4Fe–4S cluster in NapA. <i>C. jejuni</i> NapA has a conserved lysine (K79) between the Mo-cofactor and the 4Fe–4S cluster. K79 forms H-bonding interactions with the 4Fe–4S cluster and connects the latter with the Moco via an H-bonding network. Thus, it is conceivable that K79 could play an important role in the intramolecular electron transfer and the catalytic activity of NapA. In the present study, we show that the mutation of K79 to Ala leads to an almost complete loss of activity, suggesting its role in catalytic activity. The inhibition of <i>C. jejuni</i> NapA by cyanide, thiocyanate, and azide has also been investigated. The inhibition studies indicate that cyanide inhibits NapA in a non-competitive manner, while thiocyanate and azide inhibit NapA in an uncompetitive manner. Neither inhibition mechanism involves direct binding of the inhibitor to the Mo-center. These results have been discussed in the context of the loss of catalytic activity of NapA K79A variant and a possible anion binding site in NapA has been proposed.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"29 4","pages":"395 - 405"},"PeriodicalIF":2.7,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086337","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}