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Polyoxometalates bind multiple targets involved in Alzheimer’s disease 多金属氧酸盐与阿尔茨海默病相关的多个靶点结合。
IF 2.7 3区 化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-22 DOI: 10.1007/s00775-025-02111-2
Karin Ben Zaken, Rivka Bouhnik, Naama Omer, Naamah Bloch, Abraham O. Samson

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by brain aggregates of amyloid-β (Aβ) plaques and Tau tangles. Despite extensive research, effective therapy for AD remains elusive. Polyoxometalates (POMs), a class of inorganic compounds with diverse chemical structures and properties, are emerging as potential candidates for AD treatment due to their ability to target key molecular players implicated in disease pathogenesis, such as Aβ, acetylcholinesterase (AChE) and butyryl acetylcholinesterase (BChE). Here, we use molecular docking to predict the binding pose and affinities of POMs to 10 top targets associated with AD. First, we validate our method by replicating experimentally known binding of POMs to Aβ (ΔG = – 9.67 kcal/mol), AChE (ΔG = – 9.39 kcal/mol) and BChE (ΔG = – 10.86 kcal/mol). Then, using this method, we show that POM can also bind β-secretase 1 (BACE1, ΔG = – 10.14 kcal/mol), presenilin 1 (PSEN1, ΔG = – 10.65 kcal/mol), presenilin 2 (PSEN2, ΔG = – 7.94 kcal/mol), Amyloid Precursor Protein (APP, ΔG = – 7.26 kcal/mol), Apolipoprotein E (APOE4, ΔG = – 10.05 kcal/mol), Microtubule-Associated Protein Tau (MAPT, ΔG = – 5.28 kcal/mol) depending on phosphorylation, and α-synuclein (SNCA, ΔG = – 7.64 kcal/mol). Through such binding, POMs offer the potential to mitigate APP cleavage, Aβ oligomer neurotoxicity, Aβ aggregation, thereby attenuating disease progression. Overall, our molecular docking study represents a powerful tool in the discovery of POM-based therapeutics for AD, facilitating the development of novel treatments for AD.

Graphical abstract

阿尔茨海默病(AD)是一种进行性神经退行性疾病,其特征是淀粉样蛋白-β (a β)斑块和Tau缠结的大脑聚集。尽管进行了广泛的研究,但阿尔茨海默病的有效治疗方法仍然难以捉摸。多金属氧酸盐(pom)是一类具有多种化学结构和性质的无机化合物,由于其能够靶向与疾病发病机制相关的关键分子,如a β、乙酰胆碱酯酶(AChE)和丁基乙酰胆碱酯酶(BChE),正成为治疗AD的潜在候选者。在这里,我们使用分子对接来预测POMs与AD相关的10个顶级靶点的结合姿态和亲和力。首先,我们通过复制实验已知的POMs与Aβ (ΔG = - 9.67 kcal/mol)、AChE (ΔG = - 9.39 kcal/mol)和BChE (ΔG = - 10.86 kcal/mol)的结合来验证我们的方法。然后,利用这种方法,我们发现POM还可以结合β-分泌酶1 (BACE1, ΔG = - 10.14 kcal/mol)、早老素1 (PSEN1, ΔG = - 10.65 kcal/mol)、早老素2 (PSEN2, ΔG = - 7.94 kcal/mol)、淀粉样蛋白前体蛋白(APP, ΔG = - 7.26 kcal/mol)、载脂蛋白E (APOE4, ΔG = - 10.05 kcal/mol)、微管相关蛋白Tau (MAPT, ΔG = - 5.28 kcal/mol)和α-突触核蛋白(SNCA, ΔG = - 7.64 kcal/mol)。通过这种结合,POMs提供了减缓APP切割、Aβ寡聚物神经毒性、Aβ聚集的潜力,从而减缓疾病进展。总之,我们的分子对接研究是发现基于pom的阿尔茨海默病治疗方法的有力工具,促进了阿尔茨海默病新疗法的开发。
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引用次数: 0
Impacts of particles’ aspect ratio on the efficacy of β-FeOOH nanorods as nano-based oral iron supplements 颗粒长宽比对β-FeOOH纳米棒作为纳米口服铁补充剂功效的影响
IF 2.7 3区 化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-20 DOI: 10.1007/s00775-025-02110-3
Erfan Haghighatseir, Reza Heidari, Nazanin Sabet-Eghlidi, Zeinab Karimi, Aydin Berenjian, Alireza Ebrahiminezhad

Nano-iron oral supplements emerged as efficient supplements with reduced gastrointestinal side effects. Very recently, nanorods of β-FeOOH was introduced as the most efficient shape of nano-iron to be employed as oral supplement. Developed technologies in the fabrication of nanostructures provides the ability to synthesize β-FeOOH nanorods in various lengths while the other features are constant. As we all know, particles’ length has an immense impact on the biologic properties of nanorods. But there are no in vivo data about the impacts of particles length on the bioavailability and possible toxicity of β-FeOOH nanorods. So, in this study, different lengths of β-FeOOH nanorods were fabricated and employed as oral iron supplements. In this order, β-FeOOH nanorods with two lengths (mean length 50 nm and 100 nm) were successfully synthesized via hydrolysis reaction. Oral supplementation of Sprague–Dawley rats with the synthesized nanorods and FeSO4 was performed in two dosages, 10 and 20 mg/Kg. After 1-month daily treatment, blood and tissue samples were collected for hematologic, toxicologic, and pathologic analyses. Compared to FeSO4, β-FeOOH nanorods demonstrated greater efficiency to improve serum iron levels (~ threefold increase) and also hematological parameters. Similar to FeSO4, nanorods exhibited any adverse effect on liver and spleen tissues. With the same level of biocompatibility, short nanorods provided better bioavailability than the long nanorods. These data approved the short β-FeOOH nanorods as efficient and safe nanostructures to be employed in nano-based formulation of iron supplements.

Graphical abstract

纳米铁口服补充剂是一种有效的补充剂,减少了胃肠道副作用。最近,β-FeOOH纳米棒作为最有效的纳米铁形状被引入口服补充剂。发达的纳米结构制造技术提供了在其他特征不变的情况下合成各种长度的β-FeOOH纳米棒的能力。众所周知,粒子的长度对纳米棒的生物学特性有着巨大的影响。但目前还没有关于粒子长度对β-FeOOH纳米棒的生物利用度和可能毒性影响的体内数据。因此,本研究制备了不同长度的β-FeOOH纳米棒作为口服补铁剂。依次通过水解反应成功合成了两种长度(平均长度为50 nm和100 nm)的β-FeOOH纳米棒。将合成的纳米棒和FeSO4分别口服给Sprague-Dawley大鼠10和20 mg/Kg。每日治疗1个月后,采集血液和组织样本进行血液学、毒理学和病理学分析。与FeSO4相比,β-FeOOH纳米棒在提高血清铁水平(约3倍)和血液参数方面表现出更大的效率。与FeSO4类似,纳米棒对肝脏和脾脏组织没有不良影响。在相同的生物相容性水平下,短纳米棒比长纳米棒具有更好的生物利用度。这些数据表明,短β-FeOOH纳米棒是一种高效、安全的纳米结构,可用于铁补充剂的纳米配方。
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引用次数: 0
Biochemical characterization of the self-sacrificing p-aminobenzoate synthase from Nitrosomonas europaea reveals key residues involved in selecting a Fe/Fe or Mn/Fe cofactor 欧亚硝化单胞菌自我牺牲型对氨基苯甲酸酯合成酶的生化特征揭示了参与选择铁/铁或锰/铁辅助因子的关键残基。
IF 2.7 3区 化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-13 DOI: 10.1007/s00775-025-02109-w
Spenser Stone, Logan Peters, Charlotte Fricke, W. Keith Ray, Kylie D. Allen

A noncanonical route for p-aminobenzoate (pABA) biosynthesis in select bacteria utilizes a novel self-sacrificing heme oxygenase-like domain-containing oxidase/oxygenase (HDO) superfamily member. The recently characterized self-sacrificing pABA synthase from Chlamydia trachomatis (“CADD”) requires manganese and likely employs a heterobimetallic Mn/Fe cofactor. A conserved active site tyrosine residue is cleaved from the protein backbone to serve as the substrate for pABA synthesis and a lysine residue is the amino group donor. Here, we investigated the orthologous pABA synthase from the ammonia-oxidizing bacterium, Nitrosomonas europaea, which we refer to as NePabS. Consistent with the previously studied C. trachomatis enzyme, purified NePabS produces pABA in vitro in a reaction that only requires a metal cofactor, molecular oxygen, and a reducing agent, but no other substrates. Interestingly, maximal activity was observed with the addition of only iron as opposed to manganese and iron; thus, NePabS utilizes the more traditional Fe/Fe cofactor employed by most characterized HDO superfamily members. The self-sacrificing residues were confirmed to be Tyr25 and Lys159, which are the corresponding self-sacrificing residues in the CADD reaction. Strikingly, we could switch the metal dependence (Fe/Fe to Mn/Fe) and significantly improve the activity (~ twofold) of NePabS by substituting two phenylalanine residues with tyrosine residues (F148Y/F177Y), thus rendering the enzyme more similar to CADD. These results demonstrate that these two aromatic residues play an essential role in dictating metal specificity and potentially the proposed radical translocation process that facilitates the tyrosine cleavage reaction for pABA synthesis.

Graphical abstract

在某些细菌中,对氨基苯甲酸酯(pABA)生物合成的非规范途径是利用一种新型自牺牲血红素加氧酶样结构域含氧化酶/加氧酶(HDO)超家族成员。最近从沙眼衣原体("CADD")中鉴定出的自我牺牲型 pABA 合成酶需要锰,并且很可能使用了一种异金属锰/铁辅助因子。一个保守的活性位点酪氨酸残基从蛋白质骨架上裂解,作为 pABA 合成的底物,一个赖氨酸残基则是氨基供体。在这里,我们研究了氨氧化细菌亚硝酸单胞菌(Nitrosomonas europaea)的同源 pABA 合成酶,我们称之为 NePabS。与之前研究的沙眼衣原体酶一致,纯化的 NePabS 在体外产生 pABA 的反应只需要金属辅助因子、分子氧和还原剂,而不需要其他底物。有趣的是,在只添加铁而不是锰和铁的情况下,NePabS 的活性达到最大;因此,NePabS 利用了大多数具有特征的 HDO 超家族成员所使用的更传统的铁/铁辅助因子。自我牺牲残基被确认为 Tyr25 和 Lys159,它们是 CADD 反应中相应的自我牺牲残基。令人震惊的是,通过用酪氨酸残基(F148Y/F177Y)取代两个苯丙氨酸残基,我们可以改变金属依赖性(铁/铁到锰/铁)并显著提高 NePabS 的活性(约两倍),从而使该酶与 CADD 更为相似。这些结果表明,这两个芳香族残基在决定金属特异性和潜在的自由基转位过程中起着至关重要的作用,该过程促进了 pABA 合成过程中的酪氨酸裂解反应。
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引用次数: 0
Flavin-containing siderophore-interacting protein of Shewanella putrefaciens DSM 9451 reveals common structural and functional aspects of ferric–siderophore reduction 腐坏希瓦氏菌DSM 9451的含黄素铁载体相互作用蛋白揭示了铁载体还原的共同结构和功能方面。
IF 2.7 3区 化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-13 DOI: 10.1007/s00775-025-02106-z
Inês B. Trindade, Bruno M. Fonseca, Teresa Catarino, Pedro M. Matias, Elin Moe, Ricardo O. Louro

Shewanella are bacteria widespread in marine and brackish water environments and emergent opportunistic pathogens. Their environmental versatility depends on the ability to produce numerous iron-rich proteins, mainly multiheme c-type cytochromes. Although iron plays a vital role in the versatility of Shewanella species, very few studies exist regarding the strategies by which these bacteria scavenge iron from the environment. Siderophore-mediated iron transport is a commonly employed strategy for iron acquisition, and it was identified among Shewanella spp. over two decades ago. Shewanella species produce hydroxamate-type siderophores and iron removal from these compounds can occur in the cytoplasm via Fe(III)–siderophore reduction mediated by siderophore-interacting proteins (SIPs). The genome of Shewanella putrefaciens DSM 9451 isolated from an infected child contains representatives of the two different families of SIPs: the flavin-containing siderophore reductase (SbSIP) and the iron–sulfur cluster-containing ferric–siderophore reductase (SbFSR). Here, we report their expression, purification, and further biochemical characterization of SbSIP. The structural and functional characterization of SbSIP and comparison with the homologous SIP from Shewanella frigidimarina (SfSIP) revealed similarities between these proteins including a common binding pocket for NADH, NADPH, and siderophore substrates plus a pronounced redox-Bohr effect that ensures coupled transfer of electrons and protons in the physiological pH range. These mechanistic aspects open the door for further investigations on developing drugs that interfere with the iron metabolism of these bacteria and thereby prevent their spread.

Graphical abstract

希瓦氏菌是广泛存在于海洋和咸淡水环境中的细菌和突发条件致病菌。它们在环境中的多功能性取决于产生大量富含铁的蛋白质的能力,主要是多血红素c型细胞色素。尽管铁在希瓦氏菌的多功能性中起着至关重要的作用,但关于这些细菌从环境中清除铁的策略的研究很少。铁载体介导的铁转运是一种常用的铁获取策略,二十多年前在希瓦氏菌中被发现。希瓦氏菌产生羟酸盐型铁载体,这些化合物中的铁可以在细胞质中通过铁载体相互作用蛋白(SIPs)介导的铁载体还原发生脱除。从感染儿童中分离到的腐坏希瓦氏菌DSM 9451基因组包含两个不同SIPs家族的代表:含黄素的铁载体还原酶(SbSIP)和含铁硫簇的铁载体还原酶(SbFSR)。在这里,我们报道了SbSIP的表达、纯化和进一步的生化表征。SbSIP的结构和功能特征以及与来自冷希瓦氏菌的同源SIP (SfSIP)的比较揭示了这些蛋白之间的相似性,包括NADH、NADPH和铁载体底物的共同结合袋,以及明显的氧化还原-玻尔效应,确保在生理pH范围内电子和质子的耦合转移。这些机制方面为进一步研究开发干扰这些细菌铁代谢从而阻止其传播的药物打开了大门。
{"title":"Flavin-containing siderophore-interacting protein of Shewanella putrefaciens DSM 9451 reveals common structural and functional aspects of ferric–siderophore reduction","authors":"Inês B. Trindade,&nbsp;Bruno M. Fonseca,&nbsp;Teresa Catarino,&nbsp;Pedro M. Matias,&nbsp;Elin Moe,&nbsp;Ricardo O. Louro","doi":"10.1007/s00775-025-02106-z","DOIUrl":"10.1007/s00775-025-02106-z","url":null,"abstract":"<div><p><i>Shewanella</i> are bacteria widespread in marine and brackish water environments and emergent opportunistic pathogens. Their environmental versatility depends on the ability to produce numerous iron-rich proteins, mainly multiheme <i>c</i>-type cytochromes. Although iron plays a vital role in the versatility of <i>Shewanella</i> species, very few studies exist regarding the strategies by which these bacteria scavenge iron from the environment. Siderophore-mediated iron transport is a commonly employed strategy for iron acquisition, and it was identified among <i>Shewanella</i> spp. over two decades ago. <i>Shewanella</i> species produce hydroxamate-type siderophores and iron removal from these compounds can occur in the cytoplasm via Fe(III)–siderophore reduction mediated by siderophore-interacting proteins (SIPs). The genome of <i>Shewanella putrefaciens</i> DSM 9451 isolated from an infected child contains representatives of the two different families of SIPs: the flavin-containing siderophore reductase (<i>Sb</i>SIP) and the iron–sulfur cluster-containing ferric–siderophore reductase (<i>Sb</i>FSR). Here, we report their expression, purification, and further biochemical characterization of <i>Sb</i>SIP. The structural and functional characterization of <i>Sb</i>SIP and comparison with the homologous SIP from <i>Shewanella frigidimarina</i> (<i>Sf</i>SIP) revealed similarities between these proteins including a common binding pocket for NADH, NADPH, and siderophore substrates plus a pronounced redox-Bohr effect that ensures coupled transfer of electrons and protons in the physiological pH range. These mechanistic aspects open the door for further investigations on developing drugs that interfere with the iron metabolism of these bacteria and thereby prevent their spread.</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":"30 3","pages":"241 - 255"},"PeriodicalIF":2.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00775-025-02106-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622918","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}
引用次数: 0
Author Correction: Evaluation of Au(III) complexes as Plasmodium falciparum aquaglyceroporin (PfAQP) inhibitors by in silico and in vitro methods 作者更正:评价Au(III)配合物作为恶性疟原虫aquaglyceroporin (PfAQP)抑制剂的硅中和体外方法。
IF 2.7 3区 化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-12 DOI: 10.1007/s00775-025-02108-x
Federico Balgera, Muyideen Kolapo Tijani, Johan Wennerberg, Kristina E. M. Persson, Ebbe Nordlander, Ricardo J. Ferreira
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引用次数: 0
Bismuth(III) complexes of Schiff bases derived from aliphatic amines: interaction with biomolecules and antimicrobial activity 源自脂肪族胺的希夫碱铋(III)配合物:与生物大分子的相互作用及抗菌活性。
IF 2.7 3区 化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-08 DOI: 10.1007/s00775-025-02107-y
Maxim Gvozdev, Iveta Turomsha, Nikolai Osipovich, Galina Ksendzova, Alina Khodosovskaya, Anton Siomchen, Janusz M. Dąbrowski, Natalia Loginova

Schiff bases bearing a sterically hindered phenolic moiety and their Bi(III) complexes were synthesized and characterized by physicochemical, quantum chemical, and biological methods. The compounds were screened in vitro against bacterial and yeast strains. It was found that Bi(III) complexes demonstrate higher antimicrobial activity compared to the parent ligands as well as to the commonly used drug (De-Nol®). Moreover, the antibacterial activity of investigated compounds did not directly correlate with their hemolytic activity, indicating that the antimicrobial effect of Bi(III) complexes cannot be explained solely by their membranolytic properties. Spectrofluorometric studies of the interaction of the Bi(III) complexes with plasma proteins indicate their moderate to high affinity toward BSA and hemoglobin, which is crucial for the determination of their pharmacological profile as well as toxicity assessment. Additionally, molecular docking was performed to predict the possible interaction modes and binding energies of the tested compounds at the molecular level. The results obtained may provide the basis for the design and development of novel Bi(III)-based antimicrobial agents.

Graphical abstract

采用物理化学、量子化学和生物方法合成了具有位阻酚段的席夫碱及其Bi(III)配合物。对化合物进行了体外抗细菌和酵母菌的筛选。研究发现,与母体配体和常用药物(De-Nol®)相比,Bi(III)配合物具有更高的抗菌活性。此外,所研究化合物的抗菌活性与它们的溶血活性没有直接关系,这表明Bi(III)配合物的抗菌作用不能仅仅用它们的膜溶性来解释。Bi(III)复合物与血浆蛋白相互作用的荧光光谱研究表明,它们对BSA和血红蛋白具有中等至高的亲和力,这对于确定其药理学特征和毒性评估至关重要。此外,还进行了分子对接,在分子水平上预测了被测化合物可能的相互作用模式和结合能。所得结果可为新型Bi(III)基抗菌药物的设计和开发提供依据。
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引用次数: 0
Crystal structure of ferric recombinant horseradish peroxidase 铁重组辣根过氧化物酶的晶体结构。
IF 2.7 3区 化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-07 DOI: 10.1007/s00775-025-02103-2
Mst Luthfun Nesa, Suman K. Mandal, Christine Toelzer, Diana Humer, Peter C. E. Moody, Imre Berger, Oliver Spadiut, Emma L. Raven

Horseradish peroxidase (HRP), isolated from horseradish roots, is heavily glycosylated, making it difficult to crystallize. In this work, we produced recombinant HRP in E. coli and obtained an X-ray structure of the ferric enzyme at 1.63 Å resolution. The structure shows that the recombinant HRP contains four disulphide bonds and two calcium ions, which are highly conserved in class III peroxidase enzymes. The heme active site contains histidine residues at the proximal (His 170) and distal (His 42) positions, and an active site arginine (Arg 38). Surprisingly, an ethylene glycol molecule was identified in the active site, forming hydrogen bonds with His 42 and Arg 38 at the δ-heme edge. The high yields obtained from the recombinant expression system, and the successful crystallization of the enzyme pave the way for new structural studies in the future.

Graphical abstract

辣根过氧化物酶(HRP)是从辣根中分离出来的,被严重糖基化,使其难以结晶。在这项工作中,我们在大肠杆菌中产生了重组HRP,并在1.63 Å分辨率下获得了铁酶的x射线结构。结构分析表明,重组HRP含有4个二硫键和2个钙离子,在III类过氧化物酶中高度保守。血红素活性位点包含近端(His 170)和远端(His 42)的组氨酸残基,以及一个活性位点精氨酸(Arg 38)。令人惊讶的是,在活性位点发现了一个乙二醇分子,在δ-血红素边缘与His 42和Arg 38形成氢键。重组表达体系的高产率和酶的成功结晶为未来新的结构研究铺平了道路。
{"title":"Crystal structure of ferric recombinant horseradish peroxidase","authors":"Mst Luthfun Nesa,&nbsp;Suman K. Mandal,&nbsp;Christine Toelzer,&nbsp;Diana Humer,&nbsp;Peter C. E. Moody,&nbsp;Imre Berger,&nbsp;Oliver Spadiut,&nbsp;Emma L. Raven","doi":"10.1007/s00775-025-02103-2","DOIUrl":"10.1007/s00775-025-02103-2","url":null,"abstract":"<div><p>Horseradish peroxidase (HRP), isolated from horseradish roots, is heavily glycosylated, making it difficult to crystallize. In this work, we produced recombinant HRP in <i>E. coli</i> and obtained an X-ray structure of the ferric enzyme at 1.63 Å resolution. The structure shows that the recombinant HRP contains four disulphide bonds and two calcium ions, which are highly conserved in class III peroxidase enzymes. The heme active site contains histidine residues at the proximal (His 170) and distal (His 42) positions, and an active site arginine (Arg 38). Surprisingly, an ethylene glycol molecule was identified in the active site, forming hydrogen bonds with His 42 and Arg 38 at the δ-heme edge. The high yields obtained from the recombinant expression system, and the successful crystallization of the enzyme pave the way for new structural studies in the future.</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":"30 3","pages":"221 - 227"},"PeriodicalIF":2.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00775-025-02103-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571909","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}
引用次数: 0
Extending protein-film electrochemistry across enzymology and biological inorganic chemistry to investigate, track and control the reactions of non-redox enzymes and spectroscopically silent metals 将蛋白质膜电化学扩展到酶学和生物无机化学,以研究,跟踪和控制非氧化还原酶和光谱沉默金属的反应。
IF 2.7 3区 化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-01 DOI: 10.1007/s00775-025-02105-0
Clare F. Megarity, Ryan A. Herold, Fraser A. Armstrong

Protein film electrochemistry has helped to unravel many complex reactivities of electron-transferring proteins and enzymes. A versatile descendant, the ‘Electrochemical Leaf’, offers new opportunities to extend electrochemical control to myriad enzymes that neither transfer electrons nor catalyse any redox reaction, including those dependent on spectroscopically limited, labile or other challenging metal ions. By embedding a cascade comprised of several enzymes—one of which electrochemically recycles NAD(P)(H), a second being a dehydrogenase—within a porous electrode formed from fused nanoparticles, the interconnected reactions are tightly channeled to transmit energy and information, rapidly and interactively. Under nanoconfinement, nicotinamide cofactors and cascade intermediates serve as specific current carriers, far beyond the electron itself.

Graphical abstract

蛋白膜电化学有助于揭示电子传递蛋白和酶的许多复杂反应。电化学叶 "是一种多用途的后代,它为将电化学控制扩展到既不传递电子也不催化任何氧化还原反应的各种酶提供了新的机会,包括那些依赖于光谱受限、易变或其他具有挑战性的金属离子的酶。通过将由几种酶组成的级联--其中一种酶通过电化学方式回收 NAD(P)(H),另一种酶是脱氢酶--嵌入由熔融纳米粒子形成的多孔电极中,相互关联的反应被紧密地连接起来,从而快速、互动地传输能量和信息。在纳米强化作用下,烟酰胺辅助因子和级联中间体充当了特定的电流载体,远远超过了电子本身。
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引用次数: 0
Editorial by the Chief Editor 总编辑的社论。
IF 2.7 3区 化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-27 DOI: 10.1007/s00775-025-02104-1
Nils Metzler-Nolte
{"title":"Editorial by the Chief Editor","authors":"Nils Metzler-Nolte","doi":"10.1007/s00775-025-02104-1","DOIUrl":"10.1007/s00775-025-02104-1","url":null,"abstract":"","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":"30 1","pages":"1 - 2"},"PeriodicalIF":2.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00775-025-02104-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514308","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}
引用次数: 0
Cytochromes P460 and c′-β: exploiting a novel fold for multiple functions 细胞色素 P460 和 c'-β:利用新型折叠实现多种功能。
IF 2.7 3区 化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-26 DOI: 10.1007/s00775-025-02102-3
Hannah R. Adams, Sotaro Fujii, Hans E. Pfalzgraf, Peter Smyth, Colin R. Andrew, Michael A. Hough

Two related classes of ligand-binding heme c-containing proteins with a high degree of structural homology have been identified and characterized over recent decades: cytochromes P460 (cyts P460), defined by an unusual heme-lysine cross-link, and cytochromes c′-β (cyts c′-β), containing a canonical c-heme without the lysine cross-link. The shared protein fold of the cyt P460-cyt c′-β superfamily can accommodate a variety of heme environments with entirely different reactivities. On the one hand, cyts P460 with polar distal pockets have been shown to oxidize NH2OH to NO and/or N2O via proton-coupled electron transfer. On the other hand, cyts c′-β with hydrophobic distal pockets have a proposed gas binding function similar to the unrelated, but more extensively characterized, alpha helical cytochromes c′. Recent studies have also identified ‘halfway house’ proteins (cyts P460 with non-polar heme pockets and cyts c′-β with polar distal heme pockets) with functions yet to be resolved. Here, we review the structural, spectroscopic and enzymatic properties of the cyt P460-cyt c′-β superfamily with a view to understanding the structural determinants of their different functional properties.

Graphical abstract

近几十年来,已经鉴定和表征了两类具有高度结构同源性的配体结合含血红素c的相关蛋白:细胞色素P460 (cyts P460),由不寻常的血红素-赖氨酸交联定义,细胞色素c'-β (cyts c'-β),含有典型的不含赖氨酸交联的c-血红素。cyt P460-cyt c′-β超家族的共享蛋白折叠可以适应具有完全不同反应性的各种血红素环境。一方面,具有极性远端口袋的cyts P460已被证明通过质子耦合电子转移将NH2OH氧化为NO和/或N2O。另一方面,具有疏水远端口袋的cyts c‘-β具有类似于不相关但更广泛表征的α螺旋细胞色素c’的气体结合功能。最近的研究还发现了功能尚未解决的“中途”蛋白(具有非极性血红素口袋的细胞P460和具有极性远端血红素口袋的细胞c'-β)。本文综述了cyt P460-cyt c′-β超家族的结构、光谱和酶学特性,以期了解其不同功能特性的结构决定因素。
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引用次数: 0
期刊
Journal of Biological Inorganic Chemistry
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