Biochemistry articles within Nature Chemistry

Featured

  • Review Article |

    Given its ubiquity, the importance of understanding the properties of water cannot be understated. Now, stemming from discussions at a National Science Foundation-supported workshop, this Review Article highlights where there is latent chemical space for potential collaborations between the physical and supramolecular communities, both of which are interested in how molecules interact with each other in water.

    • Paul S. Cremer
    • , Amar H. Flood
    •  & David L. Mobley

  • Article |

    Enzymes that form a metabolic pathway in which the product of one enzyme is the substrate for the next have now been shown to associate through a process of sequential, directed chemotactic movement. The extent of enzyme migration is proportional to the exposure time to the substrate gradient.

    • Xi Zhao
    • , Henri Palacci
    •  & Ayusman Sen

  • Article |

    Nonribosomal peptide synthetases (NRPSs) produce vital natural products but have proven recalcitrant to biosynthetic engineering. Now, a combination of yeast surface display and fluorescence-activated cell sorting (FACS) has been used to reprogram an L-Phe-incorporating module for β-Phe. The resulting module is highly selective and functions efficiently in NRPS pathways.

    • David L. Niquille
    • , Douglas A. Hansen
    •  & Donald Hilvert

  • Article |

    Tau aggregation is associated with Alzheimer's disease and dozens of related dementias. Now atomic structures of the aggregation-prone segment VQIINK in repeat 2 of tau have been reported. Inhibitors designed using these structures block seeding by full-length tau better than inhibitors that target the VQIVYK aggregation segment in repeat 3.

    • P. M. Seidler
    • , D. R. Boyer
    •  & D. S. Eisenberg

  • Article |

    The rate constant of DNA hybridization varies over several orders of magnitude and is affected by temperature and DNA sequence. A machine-learning algorithm that is capable of accurately predicting hybridization rate constants has now been developed. Tests with this algorithm showed that over 90% of predictions were correct to within a factor of three.

    • Jinny X. Zhang
    • , John Z. Fang
    •  & David Yu Zhang

  • Article |

    Rationally designed arrays of hydrogen bonds between aromatic oligoamide segments have now been shown to generate abiotic helix-turn-helix and unexpected dimeric and trimeric helix bundle motifs. These structures show kinetic and thermodynamic stability, and cooperative folding in nonpolar solvents.

    • Soumen De
    • , Bo Chi
    •  & Ivan Huc

  • Article |

    Despite advances in peptide synthesis techniques, explicit control over the quaternary structure of synthetic peptides has remained elusive. Now, the dynamic covalent chemistry of hydrazide- and aldehyde-containing peptides has now been shown to enable the formation of unique quaternary structures with topological diversity. Using this method, oligomers were assembled into complex structures showing dramatic enhancements of antimicrobial effectiveness versus Staphylococcus Aureus.

    • James F. Reuther
    • , Justine L. Dees
    •  & Eric V. Anslyn

  • Article |

    Current mineral-based theories do not fully address how enzymes emerged from prebiotic catalysts. Now, iron–sulfur clusters can be synthesized by UV-light-mediated photolysis of organic thiols and photooxidation of ferrous ions. Iron–sulfur peptides may have formed easily on early Earth, facilitating the emergence of iron–sulfur-cluster-dependent metabolism.

    • Claudia Bonfio
    • , Luca Valer
    •  & Sheref S. Mansy

  • Article |

    The oxidative prowess of cytochrome P450s has been suggested to stem from the electron-donating axial ligand. Now, a selenocysteine-ligated P450 compound I has been trapped and characterized providing an avenue to examine this hypothesis. Measurements reveal that the selenolate-ligated compound I cleaves C–H bonds more rapidly than the wild-type equivalent.

    • Elizabeth L. Onderko
    • , Alexey Silakov
    •  & Michael T. Green

  • Article |

    The intermolecular amination of C–H bonds is an enabling transformation for the synthesis of nitrogen-containing molecules; however, developing catalysts for this class of reactions is very challenging. Now, an iron-based enzyme for this reaction has been engineered, demonstrating that a protein can confer a difficult new function upon an otherwise unreactive base metal.

    • Christopher K. Prier
    • , Ruijie K. Zhang
    •  & Frances H. Arnold

  • Article |

    The trapping of antibodies in endosomes often limits their use for intracellular targeting. Now, a single amino acid substitution on a spider-venom peptide has been shown to attenuate the cell membrane lytic activity and enables the selective rupturing of endosomal membranes. The peptide can be used to facilitate the escape of antibodies from endosomes into the cytosol.

    • Misao Akishiba
    • , Toshihide Takeuchi
    •  & Shiroh Futaki

  • Article |

    Berkelium is the only transplutonium element predicted to be able to exhibit both +III and +IV oxidation states in solution. Bk(IV) has now been stabilized through chelation with a siderophore derivative. The resulting neutral coordination compound was characterized and compared with the negatively charged species obtained by chelation of neighbouring trivalent actinides.

    • Gauthier J.-P. Deblonde
    • , Manuel Sturzbecher-Hoehne
    •  & Rebecca J. Abergel

  • Article |

    The self-propagation of misfolded conformations of tau occurs in neurodegenerative diseases, including Alzheimer's disease. The microtubule-binding region, tau244-372, reproduces much of the aggregation behaviour of tau in cells and animal models. Now, it has been shown that a 31-residue peptide from tau's R3 domain forms a cross-β conformation that efficiently seeds aggregation of tau244-372 in cells.

    • Jan Stöhr
    • , Haifan Wu
    •  & William F. DeGrado

  • News & Views |

    Biomimetic molecules that can be easily tailored offer numerous opportunities. Now, boron-based clusters have been shown to be excellent biomimetics. The ease with which the cluster surfaces can be modified stands to change how chemists might go about preparing materials for imaging, drug delivery and other applications.

    • Marek B. Majewski
    • , Ashlee J. Howarth
    •  & Omar K. Farha

  • Article |

    Lysine-rich peptides from the ribosomal core and derived homolysine decapeptides of either L-, D- or mixed chirality have now been shown to enhance RNA polymerase ribozyme activity at low magnesium concentrations, accelerate ribozyme evolution and enable templated RNA synthesis within membranous protocells.

    • Shunsuke Tagami
    • , James Attwater
    •  & Philipp Holliger

  • Article |

    Radical SAM enzymes are versatile enzymes catalysing chemically challenging reactions. Now, a radical SAM enzyme that post-translationally modifies ribosomally synthesized peptides to contain D-amino acids has been discovered in Bacillus subtilis, and its mechanism has been deciphered. These peptides, called epipeptides, efficiently inhibit bacterial growth.

    • Alhosna Benjdia
    • , Alain Guillot
    •  & Olivier Berteau

  • Article |

    Mono-iron hydrogenase promotes the heterolytic cleavage of H2 and subsequent hydride transfer to its organic substrate, H4MPT+, which serves as a CO2 ‘carrier’ in methanogenic pathways. Now, using an anthracene-scaffold-based approach, a synthetic model featuring enzyme-like Fe-C,N,S facial coordination has been developed. The model complex enables the bidirectional activity of H2 activation and evolution.

    • Junhyeok Seo
    • , Taylor A. Manes
    •  & Michael J. Rose

  • Article |

    Nature has evolved a variety of different mechanisms to generate chemical diversity; however, the reactions responsible for generating such diverse chemical libraries are often not clear. Now, the mechanisms employed by entomopathogenic bacteria for the biosynthesis of a large family of bioactive peptides have been identified. These include substrate promiscuity, enzyme cross-talk and enzyme stoichiometry.

    • Xiaofeng Cai
    • , Sarah Nowak
    •  & Helge. B. Bode

  • Article |

    Polytheonamides are giant peptide toxins produced by the uncultivated sponge bacterium Entotheonella factor. The biosynthesis of polytheonamides involves up to 50 post-translational modifications. Now, heterologous expression in Escherichia coli and Rhizobium hosts have shown that a minimalistic, iterative enzyme set introduces this exceptional molecular complexity via epimerizations, C-/N-methylations, hydroxylations, dehydration and proteolytic maturation.

    • Michael F. Freeman
    • , Maximilian J. Helf
    •  & Jörn Piel

  • Article |

    Genetic circuits are important for synthetic biology, biochemistry and bioengineering. Now, the encapsulation of genetic circuits into liposomes has been shown to enable a more modular design, the selective isolation of reactions from the environment and from each other, and the hierarchical assembly of reaction products.

    • Katarzyna P. Adamala
    • , Daniel A. Martin-Alarcon
    •  & Edward S. Boyden

  • Article |

    Biomolecular nanoscale compartments are ubiquitous in living systems. Although their formation is fairly straightforward, the same cannot be said of their inorganic counterparts. In this study, uniform nanoshells are observed self-assembling from stabilizer-free inorganic nanoparticles in water, under ambient conditions, and without the need for spherical tiling. This enables further study of inorganic prebiotic systems and compartmentalized biomimetic catalysis.

    • Ming Yang
    • , Henry Chan
    •  & Nicholas A. Kotov

  • Article |

    Despite decades of research into heme-copper oxidases, the advantages provided by copper over iron as the non-heme metal has remained unclear. Now, the preference of copper over iron has finally been explained. Copper favours faster electron transfer and higher O–O bond activation, which results in much higher oxidase activity than would be achieved by an iron equivalent.

    • Ambika Bhagi-Damodaran
    • , Matthew A. Michael
    •  & Yi Lu

  • Article |

    A chemical proteomic strategy is described for the discovery of protein-bound electrophilic groups in human cells. Using this approach, the dynamic regulation of the pyruvoyl catalytic cofactor in S-adenosyl-L-methionine decarboxylase was characterized and an N-terminal glyoxylyl modification on secernin proteins was discovered.

    • Megan L. Matthews
    • , Lin He
    •  & Benjamin F. Cravatt

  • Article |

    An unanswered question in the RNA world scenario is how sequence information could be transferred during replication of duplex RNA. Without the aid of sophisticated enzymes, strand reannealing occurs more quickly than template-directed synthesis. Now, a plausible prebiotic solution to this problem is presented, in which a viscous solvent enables information transfer from a gene-length double-stranded template.

    • Christine He
    • , Isaac Gállego
    •  & Nicholas V. Hud

  • Article |

    There is increasing evidence that highly dynamic, polydisperse peptide oligomers are the toxic species in amyloid-related diseases such as Alzheimer's and Parkinson's. Now, the secondary structure of individual amyloid oligomers has been analysed directly for the first time using a combination of ion-mobility spectrometry–mass spectrometry and gas-phase infrared spectroscopy.

    • Jongcheol Seo
    • , Waldemar Hoffmann
    •  & Kevin Pagel

  • Article |

    Difficulties in experimentally achieving simultaneous structural sensitivity and time resolution have hindered the real-time mapping of the vibrational energy relaxation pathways in biomacromolecules. Now, using ultrashort light pulses to locally deposit excess energy in a protein-bound haem, the temporal evolution of the subsequent energy flow has been monitored, unravelling vibrational couplings that lead to mode-specific temperature changes.

    • C. Ferrante
    • , E. Pontecorvo
    •  & T. Scopigno

  • Article |

    An artificial aldolase has been optimized using an ultrahigh-throughput microfluidic screening assay. The evolved enzyme exhibits excellent stereoselectivity and broad substrate scope. Structural studies suggest that a Lys-Tyr-Asn-Tyr catalytic tetrad, which emerged during directed evolution, is responsible for the >109 rate enhancement achieved by this catalyst.

    • Richard Obexer
    • , Alexei Godina
    •  & Donald Hilvert

  • Article |

    FeFe hydrogenases are highly efficient H2 producing enzymes; however, they can be inactivated by O2. Now, a mechanism for O2 diffusion within FeFe hydrogenases and its reactions at the active site of the enzyme has been proposed. These findings could help with the design of hydrogenase mutants with increased resistance to oxidative damage.

    • Adam Kubas
    • , Christophe Orain
    •  & Christophe Léger

  • Article |

    G proteins are the key mediators of G protein-coupled receptor signalling, facilitating a number of important physiological processes. Now, the total synthesis and structure–activity relationship studies have been reported for the only known selective Gq protein inhibitors, the natural cyclic depsipeptides YM-254890 and FR900359.

    • Xiao-Feng Xiong
    • , Hang Zhang
    •  & Kristian Strømgaard

  • Article |

    A motif was identified in the scaffold of an (S)-selective transaminase that enables the asymmetric synthesis of bulky chiral amines. This motif is transferable to other enzymes with as low as 70% sequence identity. The biocatalysts developed show high stereoselectivity and their synthetic potential was confirmed in preparative scale synthesis.

    • Ioannis V. Pavlidis
    • , Martin S. Weiß
    •  & Uwe T. Bornscheuer

  • Article |

    Identifying a non-enzymatic method of replicating RNA for multiple cycles has been problematic because rapid strand reannealing outcompetes slow non-enzymatic template copying. Now, oligoarginine peptides have been shown to inhibit reannealing while still allowing short primers and activated monomers to bind to the template strand, facilitating the next round of template copying.

    • Tony Z. Jia
    • , Albert C. Fahrenbach
    •  & Jack W. Szostak

  • Article |

    Selectively degrading the pathogenic, aggregated amyloid state of proteins, without affecting the functional state, is a potential therapeutic strategy for treating amyloid diseases. Now, photooxygenation catalysts that are active only when bound to the cross-β-sheet structure of the amyloid form have been developed.

    • Atsuhiko Taniguchi
    • , Yusuke Shimizu
    •  & Motomu Kanai

  • Editorial |

    Nitric oxide (NO) is an important signalling molecule in biological systems, but it is unclear exactly how it interacts with some metalloproteins. Now, a collection of articles in this issue reveal how NO binds to proteins containing type-1 copper sites.

  • News & Views |

    Nitric oxide (NO) has important functions in all forms of life and serves, for example, as a signalling molecule in mammals. Now, two complementary studies have uncovered how NO binds to blue copper proteins. This research suggests a mechanism by which NO could regulate the activity of blue copper proteins involved in denitrification.

    • Subhra Samanta
    •  & Nicolai Lehnert

  • Article |

    Dynamic nonlinear biochemical circuits are functionally rich; however, this nonlinear nature also makes programming them delicate and painstaking. Now a droplet microfluidic platform reveals precisely the bifurcations of two canonical systems: a bistable switch and a predator–prey oscillator, exposing optimal regions and mechanistic insights that inform the design of these systems.

    • A. J. Genot
    • , A. Baccouche
    •  & Y. Rondelez

  • Article |

    Cell-sized asymmetric giant lipid vesicles containing a very small amount of organic solvent have now been formed via inhomogeneous break-up of a lipid microtube that was generated by applying a jet flow to an asymmetric planar lipid bilayer. The asymmetric giant vesicles were used to investigate the dynamic responses of lipid molecules and the effect of asymmetry on biochemical reactions.

    • Koki Kamiya
    • , Ryuji Kawano
    •  & Shoji Takeuchi

  • Article |

    A temperature-dependent kinetic study of ground-state proton transfer in the green fluorescent protein highlights the role of ‘deep tunnelling’ in proton wires. A potential mechanism for directional proton transport is proposed, where high-pKa amino acid residues act as ‘tunnel diodes’ and as stabilizing elements within protein water wires.

    • Bridget Salna
    • , Abdelkrim Benabbas
    •  & Paul M. Champion

  • News & Views |

    The low-complexity-protein, liquid phases of membraneless organelles have now been established to selectively partition biomolecules. The specialized microenvironment that they provide differs chemically from the surrounding medium and enables specific nucleic-acid remodelling reactions.

    • James Shorter

  • Article |

    NO participates in numerous physiological processes of which many involve the reaction of NO with metalloenzymes to form a metal–nitrosyl (M–NO). Now, addition of NO to models of type 1 Cu sites has provided a fully characterized S-nitrosothiol adduct, [CuI](κ1-N(O)SR), that reversibly loses NO upon purging with an inert gas. These findings suggest a new motif for reversible binding of nitric oxide at bioinorganic metal centres.

    • Shiyu Zhang
    • , Marie M. Melzer
    •  & Timothy H. Warren

  • Article |

    S-Nitrosylation has emerged as an important pathway for dynamic post-translational regulation of many classes of proteins. Now, the reversible insertion of NO into a copper–thiolate bond has been observed under physiologically relevant conditions using an engineered azurin. DFT calculation indicates that the reaction proceeds via a radical combination mechanism.

    • Shiliang Tian
    • , Jing Liu
    •  & Yi Lu

  • Review Article |

    Chemical protein synthesis can enable the preparation of proteins containing post-translational modifications or unnatural variations such as D-amino acids. Such modified proteins are not easily fabricated by other methods. This Review provides an overview of the current approaches for the chemical synthesis of proteins.

    • Somasekhar Bondalapati
    • , Muhammad Jbara
    •  & Ashraf Brik

  • Article |

    Capsular polysaccharides are a protective layer enveloping pathogenic bacteria. Understanding their export could guide the design of therapeutics that render bacteria vulnerable to attack by the immune system or other therapeutic agents. Now, a synthetic strategy of polyglycosylation has been developed to obtain defined capsular polysaccharide fragments. Subsequent nanolitre detection enables their export to be studied at the single-molecule level.

    • Lingbing Kong
    • , Andrew Almond
    •  & Benjamin G. Davis

  • Review Article |

    In enzyme-catalysed metabolic pathways, substrate channelling often directs the movement of intermediates from one active site to the next. Intramolecular tunnels, electrostatic interactions and chemical swing arms pass intermediates from one enzyme to the next, enhancing pathway catalysis. Introducing mechanisms of bounded diffusion in chemical cascades can increase selectivity, transient rates and overall yield.

    • Ian Wheeldon
    • , Shelley D. Minteer
    •  & Matthew Sigman

  • Article |

    Precise control of vesicle size is highly desirable both for basic biochemical research and biomedical applications. Now, monodispersed sub-100-nm vesicles with predefined sizes have been produced using a method based on membrane self-assembly within a DNA-nanostructure guide.

    • Yang Yang
    • , Jing Wang
    •  & Chenxiang Lin

  • Article |

    A collaborative approach between experiment and simulation has revealed a single mutation in the F/G loop of the newly described nitrating cytochrome P450 TxtE that controls loop dynamics and, more surprisingly, the regioselectivity of the reaction. This mutation is present in a subset of homologous nitrating P450s that produce a previously unidentified biosynthetic intermediate, 5-nitro-L-tryptophan.

    • Sheel C. Dodani
    • , Gert Kiss
    •  & Frances H. Arnold

  • Article |

    The development of cells requires a mechanism to support homeostasis—the maintenance of constant internal conditions—as cellular growth results in internal dilution. Now, a simple physical process is described in which short oligonucleotide inhibitors enable dilution-driven activation of encapsulated ribozymes via membrane growth, suggesting homeostatic mechanisms could have existed in the earliest cells.

    • Aaron E. Engelhart
    • , Katarzyna P. Adamala
    •  & Jack W. Szostak

  • News & Views |

    Vaccination with a synthetic glycoconjugate, in combination with the administration of an inhibitor that blocks capsular polysaccharide synthesis in bacteria, could offer an alternative route to combat bacterial infections.

    • David Bundle

  • Article |

    The repertoire of amino acids available for ribosomal peptide synthesis is limited by the genetic code. Now, a method to reduce the redundancy of codons has been developed based on the artificial division of codon boxes. This method enables non-proteinogenic amino acids to be included in peptides without sacrificing proteinogenic ones.

    • Yoshihiko Iwane
    • , Azusa Hitomi
    •  & Hiroaki Suga

  • Article |

    The presence and linkage of unusual higher sugars in the ‘inner core’ of Gram-negative bacteria makes the core lipopolysacchride tetrasaccharide Hep2Kdo2 a tough target. Now, a 2+2 glycosylation strategy has facilitated the synthesis of this glycoconjugate. Synthesis of Hep2Kdo2 enabled an antibacterial vaccination strategy based on immunization with the glycoconjugate and the subsequent administration of an inhibitor that uncovers the corresponding epitope in pathogenic bacteria.

    • Lingbing Kong
    • , Balakumar Vijayakrishnan
    •  & Benjamin G. Davis

  • News & Views |

    The discovery of a tetrapeptide containing a reactive cysteine provides a method to site-selectively modify peptides and proteins, even if other cysteine residues are present in the polypeptide chain.

    • Yichao Huang
    •  & Lei Liu

Browse broader subjects

Browse narrower subjects

Browse Biochemistry across other nature.com journals