Chemical biology articles within Nature

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  • News & Views |

    With age comes wisdom, or so they say. The reality is that, with age, the ability to store memories declines. One way of tackling this problem might be to raise neuronal levels of the signalling molecule EphB2. See Article p.47

    • Robert C. Malenka
    •  & Roberto Malinow

  • News & Views |

    Computers use transistor-based logic gates as the basis of their functions, but molecular logic gates would make them much faster. A report of DNA-based logic gates could be a first step towards molecular computing.

    • Thomas Carell

  • News Feature |

    To learn the chemical language of plants, Ian Baldwin has built up a German research empire that engineers seeds — and a field station in the Utah wilderness to grow them.

    • Alison Abbott

  • Letter |

    The first X-ray crystal structure of a diterpene cyclase is reported — this enzyme, taxadiene synthase, catalyses the cyclization of an isoprenoid in the first committed step of the biosynthesis of the cancer chemotherapeutic drug Taxol. The C-terminal catalytic domain binds and activates the substrate in a manner seen in class I terpenoid cyclases, but the N-terminal domain and a third 'insertion' domain together adopt the fold of a class II terpenoid cyclase. It is proposed that this enzyme could be the ancestral progenitor of all terpenoid cyclases.

    • Mustafa Köksal
    • , Yinghua Jin
    •  & David W. Christianson

  • Article |

    Sugar efflux transporters are essential for diverse processes such as nectar production and seed and pollen development, as well for the maintenance of blood glucose levels in animals. These authors identify and characterize a novel sugar transporter family, SWEET, and show that several Arabidopsis, rice and metazoan homologues mediate glucose transport. In addition, some of these transporters are exploited by plant pathogens for nutritional gain and virulence.

    • Li-Qing Chen
    • , Bi-Huei Hou
    •  & Wolf B. Frommer

  • News & Views |

    An extension of synthetic biology to a medicinal plant involves the transfer of chlorination equipment from bacteria. This exercise adds implements to the enzymatic toolbox for generating natural products. See Letter p.461

    • Joseph P. Noel

  • Article |

    Cysteine is the most intrinsically nucleophilic amino acid in proteins, but the absence of a consensus sequence that defines functional cysteines in proteins has hindered their discovery and characterization. Here, a proteomics method to quantitatively profile the intrinsic reactivity of cysteine residues directly in native biological systems is described. Hyper-reactive cysteines were identified in several proteins of uncharacterized function, including a residue conserved across eukaryotes that is shown to be required for yeast viability and involved in iron–sulphur protein biogenesis.

    • Eranthie Weerapana
    • , Chu Wang
    •  & Benjamin F. Cravatt

  • News Feature |

    The biology is too complicated. Pharma companies are quitting. Where are schizophrenia drugs going to come from?

    • Alison Abbott

  • Letter |

    Mononuclear iron-containing oxygenases have many important roles in the cell, including the demethylation of DNA and histones. These authors crystallized the AlkB oxygenase in complex with various modified DNAs. By growing the crystals under anaerobic conditions and then exposing them to dioxygen to initiate oxidation, two different intermediates were trapped. A third type of intermediate was determined using additional computational analysis. These structures provide insight into how these enzymes perform oxidative demethylation.

    • Chengqi Yi
    • , Guifang Jia
    •  & Chuan He

  • Letter |

    Halogen atoms have been observed in several different classes of natural product, but very few halogenated natural products have been isolated from terrestrial plants. These authors show that biosynthetic machinery responsible for chlorination events in bacteria could be introduced into the medicinal plant Catharanthus roseus. Prokaryotic halogenases function within the plant cells to generate chlorinated tryptophan, which is then used by the monoterpene indole alkaloid metabolic pathways to yield chlorinated alkaloids.

    • Weerawat Runguphan
    • , Xudong Qu
    •  & Sarah E. O’Connor

  • News & Views |

    Short residence times in the bloodstream reduce the effectiveness of protein drugs. Application of an approach that combines protein and polymer engineering prolongs circulation time and increases drug uptake by tumours.

    • Jeffrey A. Hubbell

  • Letter |

    The energy-coupling factor transporters are responsible for vitamin uptake in prokaryotes. Here, the X-ray crystal structure of the membrane-embedded, substrate-binding domain of a riboflavin transporter from Staphylococcus aureus is reported. The transporter adopts a previously unreported fold and contains a riboflavin molecule bound to a loop and the periplasmic portion of several transmembrane segments.

    • Peng Zhang
    • , Jiawei Wang
    •  & Yigong Shi

  • News & Views |

    Proteins that pump a wide range of toxic compounds out of cells are ubiquitous in nature, but crystal structures for one family of these transporters have remained elusive. Until now. See Letter p.991

    • Hendrik W. van Veen

  • Letter |

    These authors identify the human enzyme responsible for menaquinone-4 biosynthesis, a naturally occurring form of vitamin K. They find that UbiA prenyltransferase containing 1, a human homologue of a prenyltransferase gene from Escherichia coli, encodes an enzyme that can convert vitamin K derivatives into menaquinone-4.

    • Kimie Nakagawa
    • , Yoshihisa Hirota
    •  & Toshio Okano

  • Letter |

    In Escherichia coli, the uptake of L-fucose, an important source of carbon for microorganisms, is mediated by a proton symporter from the major facilitator superfamily (MFS). These authors report the first X-ray crystal structure of the outward-open conformation of an MFS proton transporter, FucP. Building on previous work, they develop a working model for how the substrate is recognized by the transporter and how the protein mediates L-fucose/proton symport.

    • Shangyu Dang
    • , Linfeng Sun
    •  & Nieng Yan

  • Letter |

    Transporter proteins from the MATE (multidrug and toxic compound extrusion) family are involved in metabolite transport in plants, and in multiple-drug resistance in bacteria and mammals. Here, the X-ray crystal structure of a MATE transporter from Vibrio cholerae is reported. The structure is in an outward-facing conformation, and reveals a cation-binding site near to residues previously deemed essential for transport.

    • Xiao He
    • , Paul Szewczyk
    •  & Geoffrey Chang

  • Letter |

    PLX4032 is a selective inhibitor of the B-RAF protein that has shown promising results in an early clinical trial in melanoma patients with an activating mutation in B-RAF. Now the structure and function of this inhibitor are described. Translational data from a phase I trial show that clinical efficacy requires a substantial degree of inhibition of the ERK pathway downstream of B-RAF. The data also show that BRAF-mutant melanomas are highly dependent on B-RAF activity.

    • Gideon Bollag
    • , Peter Hirth
    •  & Keith Nolop

  • Letter |

    A central hub of carbon metabolism is the tricarboxylic acid (TCA) cycle, which serves to connect the processes of glycolysis, gluconeogenesis, respiration, amino acid synthesis and other biosynthetic pathways. These authors show that TCA metabolism in the human malaria parasite Plasmodium falciparum is largely disconnected from glycolysis and is organized along a fundamentally different architecture — not cyclic, but branched — from the canonical textbook pathway.

    • Kellen L. Olszewski
    • , Michael W. Mather
    •  & Manuel Llinás

  • Editorial |

    The controversy surrounding diabetes drugs highlights the importance of comparative studies.

  • Letter |

    Metalloproteins are important in many biological processes, including respiration, photosynthesis and drug metabolism. Using genome sequences to predict the numbers and types of metal an organism uses is currently very challenging. These authors used a proteomics approach to identify and characterize a large number of a microorganism's metalloproteins on a genome-wide scale, and successfully separated and identified its cytoplasmic metalloproteins.

    • Aleksandar Cvetkovic
    • , Angeli Lal Menon
    •  & Michael W. W. Adams

  • News & Views |

    Amide bonds connect the amino acids in proteins and occur in many other useful molecules. An amide-forming reaction that turns the conventional approach on its head offers a practical way of making these bonds.

    • Karl Scheidt

  • Letter |

    Network theory has become pervasive in all sectors of biology, from biochemical signalling to human societies, but identification of relevant functional communities has been impaired by many nodes belonging to several overlapping groups at once, and by hierarchical structures. These authors offer a radically different viewpoint, focusing on links rather than nodes, which allows them to demonstrate that overlapping communities and network hierarchies are two faces of the same issue.

    • Yong-Yeol Ahn
    • , James P. Bagrow
    •  & Sune Lehmann

  • Article |

    Translation elongation factor 2 (EF2) from archaea and eukaryotes contains a unique, post-translationally modified histidine residue called diphthamide, which is the target of diphtheria toxin. The biosynthesis of diphthamide involves three steps; here it is shown that the first step in the archaeon Pyrococcus horikoshii requires an unusual iron–sulphur-cluster enzyme, Dph2. It catalyses unprecedented chemistry.

    • Yang Zhang
    • , Xuling Zhu
    •  & Hening Lin

  • Column |

    Claims of 'synthetic life' reflect only our changing conception of what life is and how it might be made, says Philip Ball.

    • Philip Ball

  • Letter |

    Copper is an essential trace element for eukaryotes and most prokaryotes, but it has toxic side effects, so the levels of intracellular free copper must be limited. Mass spectrometry has now been used to measure the apparent Cu(I)-binding affinities of a representative set of intracellular copper proteins involved in redox catalysis, in copper trafficking to and within different cellular compartments, and in copper storage. The results provide the thermodynamic basis for the kinetic processes that lead to the distribution of cellular copper.

    • Lucia Banci
    • , Ivano Bertini
    •  & Peep Palumaa

  • Technology Feature |

    The scientific community now seems convinced that small RNAs will become therapies, if new tools can help these large molecules to make it safely into cells. Monya Baker reports.

    • Monya Baker

  • Letter |

    Particulate methane monooxygenase (pMMO) is an integral membrane protein, found in methanotropic bacteria, that can selectively oxidize methane to produce methanol. This metalloenzyme contains three subunits, and the metal composition and exact location of its active site has been the subject of much speculation. Here it is found that the enzyme's activity is dependent on copper, and that the active site is located in the soluble domains of the pmoB subunit.

    • Ramakrishnan Balasubramanian
    • , Stephen M. Smith
    •  & Amy C. Rosenzweig

  • Letter |

    GABAB receptors are the G-protein-coupled receptors for γ-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain. Here, functional proteomics is used to show that GABAB receptors in the brain are complexes of GABAB1, GABAB2 and members of a subfamily of KCTD proteins. The KCTD proteins increase the potency of agonists and markedly alter the G-protein signalling of the receptors, suggesting that they determine the pharmacology and kinetics of the receptor response.

    • Jochen Schwenk
    • , Michaela Metz
    •  & Bernhard Bettler

  • Letter |

    The four receptors of the Notch family are transmembrane proteins through which mammalian cells communicate to regulate cell fate and growth. Aberrant signalling through each receptor has been linked to disease, so the Notch pathway is a compelling drug target. But current drugs cannot distinguish between the different Notch proteins. Here, phage display technology has been used to generate highly specialized antibodies, enabling the functions of Notch1 and Notch2 to be discriminated in humans and mice.

    • Yan Wu
    • , Carol Cain-Hom
    •  & Christian W. Siebel

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