Bioinorganic chemistry

  • Article
    | Open Access

    The “anti-branching rule”, introduced in 1950, excludes branched polyphosphates from biological relevance due to their supposedly rapid hydrolysis. Here, the authors synthesize monodisperse branched polyphosphates and demonstrate their unexpected stability in water, as well as provide evidence for their competence in phosphorylation.

    • Tobias Dürr-Mayer
    • , Danye Qiu
    •  & Henning J. Jessen
  • Article
    | Open Access

    Sonodynamic therapy has therapeutic promise due to its safety and good tissue penetration, but is currently bottlenecked due to a lack of efficient and safe sonosensitizers. Here the authors show that [Ru(bpy)3]2+ can produce singlet oxygen and sonooxidize NADH in deep tissue, and destroy mouse tumors effectively.

    • Chao Liang
    • , Jiaen Xie
    •  & Pingyu Zhang
  • Article
    | Open Access

    Heme biosynthesis depends on iron-sulfur (Fe-S) cluster biogenesis but the molecular connection between these pathways is not fully understood. Here, the authors show that the heme biosynthesis enzyme ALAD contains an Fe-S cluster, disruption of which reduces ALAD activity and heme production in human cells.

    • Gang Liu
    • , Debangsu Sil
    •  & Tracey Ann Rouault
  • Article
    | Open Access

    The sulfur-reducing enzyme MBS and the hydrogen-gas evolving MBH are the evolutionary link between the ancestor Mrp antiporter and the mitochondrial respiratory complex I. Here, the authors characterise MBS from the hyperthermophilic archaeon Pyrococcus furiosus, solve its cryo-EM structure and discuss the structural evolution from Mrp to MBH and MBS and to the modern-day complex I.

    • Hongjun Yu
    • , Dominik K. Haja
    •  & Michael W. W. Adams
  • Article
    | Open Access

    Photosensitizers that  are stable in biological conditions with absorption in the biological spectral window are needed for photodynamic therapy. Here, the authors report on the development of a Ruthenium complex for 1 and 2-photon therapy to address these issues and demonstrate application in vivo.

    • Johannes Karges
    • , Shi Kuang
    •  & Gilles Gasser
  • Article
    | Open Access

    Many metalloenzymes are highly specific for their cognate metal ion but the molecular principles underlying this specificity often remain unclear. Here, the authors characterize the structural and biochemical basis for the different metal specificity of two evolutionarily related superoxide dismutases.

    • Anna Barwinska-Sendra
    • , Yuritzi M. Garcia
    •  & Kevin J. Waldron
  • Article
    | Open Access

    Understanding enzyme active sites can elucidate fundamental enzymatic reaction pathways and inform designs for synthetic catalysts. Here, authors employ operando X-ray absorption spectroelectrochemistry to assess copper ions in bilirubin oxidase during oxygen reduction electrocatalysis.

    • Lucyano J. A. Macedo
    • , Ayaz Hassan
    •  & Frank N. Crespilho
  • Article
    | Open Access

    Mobile group II introns function as ribozymes to splice and reinsert themselves into DNA, thereby colonizing new genomic regions. Here the authors use single-molecule FRET and molecular dynamics simulations to reveal a structural link between metal ion induced kinetic heterogeneity and the sugar puckers at the exon-intron binding interface.

    • Fabio D. Steffen
    • , Mokrane Khier
    •  & Roland K. O. Sigel
  • Article
    | Open Access

    Iron is essential for growth of Mycobacterium tuberculosis, but most of the iron in the human body is stored in heme within hemoglobin. Here, Mitra et al. identify two heme uptake mechanisms in M. tuberculosis, one dependent on the inner-membrane Dpp importer and the other dependent on host albumin.

    • Avishek Mitra
    • , Ying-Hui Ko
    •  & Michael Niederweis
  • Article
    | Open Access

    Metallo-β-lactamases (MBLs) confer resistance to carbapenem antibiotics. Here, López et al. show that the host range of MBLs depends on the efficiency of MBL signal peptide processing and secretion into outer membrane vesicles, which affects bacterial fitness.

    • Carolina López
    • , Juan A. Ayala
    •  & Alejandro J. Vila
  • Article
    | Open Access

    The mechanism of iron-sulfur (Fe-S) cluster biosynthesis is not fully understood. Here, the authors develop a physiologically relevant in vitro model of Fe-S cluster assembly, allowing them to elucidate the sequence of Fe-S cluster synthesis along with the respective roles of ferredoxin-2 and frataxin.

    • Sylvain Gervason
    • , Djabir Larkem
    •  & Benoit D’Autréaux
  • Article
    | Open Access

    In vivo decorporation of U(VI) from bones is an unsolved challenge because of the formation of stable uranium phosphate complexes. Here, the authors develop a hydroxypyridonone-based ligand with strong uranium complexation and low cytotoxicity. They find this ligand effectively removes uranium from kidney and bones in mice, and is suitable for oral administration.

    • Xiaomei Wang
    • , Xing Dai
    •  & Shuao Wang
  • Article
    | Open Access

    The activity of the membrane-bound enzyme pMMO depends on copper but the location of the copper centers is still under debate. Here, the authors reconstitute pMMO in nanodiscs and use native top-down MS to localize its copper centers, providing insights into which sites are essential for activity.

    • Soo Y. Ro
    • , Luis F. Schachner
    •  & Amy C. Rosenzweig
  • Article
    | Open Access

    Studying the electronic structures and spin transitions of synthetic heme analogs is crucial to advancing our understanding of heme enzyme mechanisms. Here the authors show that a Co(II) porphyrin complex undergoes an unexpected spin state transition upon deprotonation of its axial imidazole ligand.

    • Jianping Zhao
    • , Qian Peng
    •  & Jianfeng Li
  • Article
    | Open Access

    The diheme enzyme MauG forms a bis-Fe(IV) state. Here the authors identify and determine the structure of BthA, a diheme peroxidase conserved in all Burkholderia and show that BthA also forms a bis-Fe(IV) species but mechanistically differs from MauG by combining magnetic resonance, near-IR and Mössbauer spectroscopies and electrochemical methods.

    • Kimberly Rizzolo
    • , Steven E. Cohen
    •  & Sean J. Elliott
  • Article
    | Open Access

    FeV(O)(OH) species have long been thought to play a role in a range of enzymatic oxidations, but their characterization has remained elusive. Here, using gas-phase ion spectroscopy, the authors characterize an FeV(O)(OH) species and find that its reactivity mimics that of Rieske oxygenases.

    • Margarida Borrell
    • , Erik Andris
    •  & Miquel Costas
  • Article
    | Open Access

    Tetrathiomolybdate (TM) and Cu-ATPases, e.g. Wilson (WLN) protein, affect the efficacy of common anticancer drug cisplatin. Here, the authors show that TM generates a protein dimer with a WLN domain by expelling copper and provide insight into the synergy of TM and cisplatin in cancer chemotherapy.

    • Tiantian Fang
    • , Wanbiao Chen
    •  & Yangzhong Liu
  • Article
    | Open Access

    Controlled switching of the spin state of transition metal ions is key in many enzymatic reactions, but difficult to replicate in synthetic systems. Here the authors report on an iron(III) porphyrin with a photochromic axial ligand that, in solution, reversibly switches between low-spin and high-spin upon irradiation with two different wavelengths.

    • Sreejith Shankar
    • , Morten Peters
    •  & Rainer Herges
  • Article
    | Open Access

    Myoglobin bound to carbon monoxide undergoes an ultrafast light-induced reaction, which ends up in a photolyzed carbon monoxide and a spin transition of the iron center. Here, the authors employ quantum wavepacket dynamics to show that photolysis precedes the spin transition, a mechanism dominated by strong electron-nuclear couplings.

    • Konstantin Falahati
    • , Hiroyuki Tamura
    •  & Miquel Huix-Rotllant
  • Article
    | Open Access

    Methane- and ammonia-oxidizing bacteria use the integral membrane, copper-dependent enzymes particulate methane monooxygenase (pMMO) and ammonia monooxygenase (AMO) to oxidize methane and ammonia. Here the authors structurally characterize the copper-binding protein PmoD, which contains an unusual CuA site and their genetic analyses strongly support a pMMO and AMO related function of PmoD.

    • Oriana S. Fisher
    • , Grace E. Kenney
    •  & Amy C. Rosenzweig
  • Article
    | Open Access

    Nitrogenase—whose cofactor consists of a metal–sulfur cluster—catalyzes the production of NH3 from N2, but designing metal–sulfur complexes capable of promoting this conversion remains challenging. Here, the authors report on the activation of N2 by a metal–sulfur cluster containing [Mo3S4Ti] cubes, demonstrating NH3 and N2H4 production.

    • Yasuhiro Ohki
    • , Keisuke Uchida
    •  & Takehiro Ohta
  • Article
    | Open Access

    Cytochrome c oxidase (CytcO) is the last enzyme of the electron transport chain, but how the electrochemical membrane potential affects CytcO is unclear. Here the authors show that proton uptake to the catalytic site of CytcO and presumably proton translocation was impaired by the potential, but electron transfer was not affected.

    • Markus L. Björck
    •  & Peter Brzezinski
  • Article
    | Open Access

    NifB is a key enzyme in the biosynthesis pathway of the nitrogenase FeMo cofactor. Here, the authors investigate the maturation of its iron-sulfur clusters by EPR and biochemical analyses, showing how individual precursor clusters participate in the formation of the final iron-sulfur cluster.

    • Lee A. Rettberg
    • , Jarett Wilcoxen
    •  & Yilin Hu
  • Article
    | Open Access

    Bacteria possess transcription factors whose DNA-binding activity is altered upon binding to specific metals, but the binding of metals is not specific in vitro. Here, Osman et al. show that tight regulation of buffered intracellular metal concentrations is a prerequisite for metal specificity.

    • Deenah Osman
    • , Andrew W. Foster
    •  & Nigel J. Robinson
  • Article
    | Open Access

    Significant challenges exist for structural characterization of enzymes responsible for biomineralization. Here the authors show that native mass spectrometry and high resolution electron microscopy can define the subunit topology and copper binding of a manganese oxidizing complex, and describe early stage formation of its mineral products

    • Christine A. Romano
    • , Mowei Zhou
    •  & Bradley M. Tebo
  • Article
    | Open Access

    Carbapenem-resistant bacteria pose a major health threat by expressing metallo-β-lactamases (MβLs), enzymes able to hydrolyse these life-saving drugs. Here the authors use biophysical and computational methods and show that different MβLs share the same reaction mechanism, suggesting new strategies for drug design.

    • María-Natalia Lisa
    • , Antonela R. Palacios
    •  & Alejandro J. Vila
  • Article
    | Open Access

    Lanthanide elements are difficult to separate from aqueous solution with low energy input. Here, the authors design a peptide that recognizes and drives the precipitation of an insoluble lanthanide complex under physiological conditions, introducing a biomineralization-based approach for rare earth recovery.

    • Takaaki Hatanaka
    • , Akimasa Matsugami
    •  & Nobuhiro Ishida
  • Article
    | Open Access

    The mitochondrial proteins ISCA1 and ISCA2 form a complex that is involved in the biogenesis of Fe–S clusters. Here the authors report that ISCA1 and ISCA2 interact differently with proteins of the Fe–S machinery and that under certain conditions, ISCA2 seems dispensable for Fe–S biogenesis.

    • Lena Kristina Beilschmidt
    • , Sandrine Ollagnier de Choudens
    •  & Alain Martelli
  • Article
    | Open Access

    Chiral structures are formed in numerous processes including biomineralization of calcium carbonate. Here, the authors demonstrate that the chiral, hierarchically-organized architecture of the calcium carbonate mineral, vaterite, can be controlled simply by the addition of chiral acidic amino acids.

    • Wenge Jiang
    • , Michael S. Pacella
    •  & Marc D. McKee
  • Article
    | Open Access

    Terminal CoIV-oxo species are key intermediates in various cobalt-mediated oxidation reactions, but little is known about their chemical properties. Here the authors generate and isolate a mononuclear non-haem CoIV-O complex and analyse its structure and reactivity towards a range of catalytic transformations.

    • Bin Wang
    • , Yong-Min Lee
    •  & Wonwoo Nam
  • Article
    | Open Access

    Proteins can template the synthesis of inorganic nanoparticles, but the formation mechanisms remain vague. Here, the authors directly observe, through a sequence of X-ray crystal structures, the stages of gold sub-nanocluster growth within the confined environment of a ferritin cage.

    • Basudev Maity
    • , Satoshi Abe
    •  & Takafumi Ueno
  • Article
    | Open Access

    Proton pumps that are driven by light to pump protons out of the cell are involved in the conversion of sunlight into proton motive force; pumps to drive protons in the other direction have been engineered. Here, the authors report the identification and characterisation of a naturally occurring inward-driven protein pump.

    • Keiichi Inoue
    • , Shota Ito
    •  & Hideki Kandori
  • Article
    | Open Access

    High levels of homocysteine in cells are linked to pathological states. Here, the authors report that homocysteine inactivates catalase by modifying the heme group, impairing cellular redox homeostasis, and show that this modification occurs in cancer cells and in a cellular model of Parkinson’s disease.

    • Dominique Padovani
    • , Assia Hessani
    •  & Isabelle Artaud
  • Article
    | Open Access

    Pathogenic bacteria acquire iron from heme cofactors imported by ABC heme transporters. Here the authors present crystal structures of Burkholderia cenocepaciaheme importer BhuUV with and without the heme-binding protein BhuT, gathering mechanistic insight into the catalytic cycle of heme import.

    • Youichi Naoe
    • , Nozomi Nakamura
    •  & Hiroshi Sugimoto
  • Article
    | Open Access

    The inorganic procoagulant polymer polyphosphate participates in thrombosis via factor XII. Here the authors use recombinant probes that specifically bind or degrade circulating polyphosphate to protect mice in arterial and venous thrombosis models without an increased bleeding risk, the primary complication of all currently used anticoagulants.

    • Linda Labberton
    • , Ellinor Kenne
    •  & Thomas Renné
  • Article
    | Open Access

    Mutations in the extracellular domain of zinc transporter ZIP4 result in a lethal disorder. Here, the authors report the first crystal structure of ZIP4 extracellular domain, unveiling its unprecedented dimerization and two structural independent subdomains that have crucial roles in zinc transport.

    • Tuo Zhang
    • , Dexin Sui
    •  & Jian Hu
  • Article
    | Open Access

    Mep2 proteins are tightly regulated fungal ammonium transporters. Here, the authors report the crystal structures of closed states of Mep2 proteins and propose a model for their regulation by comparing them with the open ammonium transporters of bacteria.

    • Bert van den Berg
    • , Anupama Chembath
    •  & Julian C. Rutherford
  • Article
    | Open Access

    The Na+,K+-ATPase moves three Na+ ions out of the cell and transfers two K+ ions in the opposite direction. Here the authors use X-ray crystallography to look at the substitution of two bound K+with those in the medium and show that it occurs sequentially through a narrow gate.

    • Haruo Ogawa
    • , Flemming Cornelius
    •  & Chikashi Toyoshima
  • Article
    | Open Access

    Artificial metalloenzymes (ArMs) have the potential to improve transition metal reactivity in complex media. Here, the authors link a dirhodium catalyst to a prolyl oligopeptidase to create an ArM that catalyzes enantioselective olefin cyclopropanation in aqueous solution.

    • Poonam Srivastava
    • , Hao Yang
    •  & Jared C. Lewis
  • Article
    | Open Access

    The investigation of the chemical reactivity of metal centres in metalloproteins in aqueous solution is challenging. Here, the authors demonstrate the use of single molecule force spectroscopy to study the chemical reactivity of the iron-sulfur centre in rubredoxin in aqueous solution.

    • Peng Zheng
    • , Guilherme M. Arantes
    •  & Hongbin Li
  • Article
    | Open Access

    Carotenes are naturally abundant, widely studied unsaturated hydrocarbon pigments but their metal-binding ability has been virtually unexplored. Here, the authors demonstrate that they can be used to reversibly assemble and align homo- and hetero-metallic decanuclear chain complexes.

    • Shinnosuke Horiuchi
    • , Yuki Tachibana
    •  & Tetsuro Murahashi
  • Article |

    Malaria parasites generate metabolic energy through anaerobic glycolysis, yielding lactate and protons that are then secreted out of the parasite cell by an unknown transporter. Here, the authors identify and characterize a lactate/proton transporter that may be carrying out such function in Plasmodium.

    • Binghua Wu
    • , Janis Rambow
    •  & Eric Beitz