Multidrug and toxic compound extrusion (MATE) family transporters are conserved in the three primary domains of life (Archaea, Bacteria and Eukarya), and export xenobiotics using an electrochemical gradient of H(+) or Na(+) across the membrane. MATE transporters confer multidrug resistance to bacterial pathogens and cancer cells, thus causing critical reductions in the therapeutic efficacies of antibiotics and anti-cancer drugs, respectively. Therefore, the development of MATE inhibitors has long been awaited in the field of clinical medicine. Here we present the crystal structures of the H(+)-driven MATE transporter from Pyrococcus furiosus in two distinct apo-form conformations, and in complexes with a derivative of the antibacterial drug norfloxacin and three in vitro selected thioether-macrocyclic peptides, at 2.1-3.0 Å resolutions. The structures, combined with functional analyses, show that the protonation of Asp 41 on the amino (N)-terminal lobe induces the bending of TM1, which in turn collapses the N-lobe cavity, thereby extruding the substrate drug to the extracellular space. Moreover, the macrocyclic peptides bind the central cleft in distinct manners, which correlate with their inhibitory activities. The strongest inhibitory peptide that occupies the N-lobe cavity may pave the way towards the development of efficient inhibitors against MATE transporters.

Invariance under the charge, parity, time-reversal (CPT) transformation 1 is one of the fundamental symmetries of the standard model of particle physics. This CPT invariance implies that the fundamental properties of antiparticles and their matter-conjugates are identical, apart from signs. There is a deep link between CPT invariance and Lorentz symmetry-that is, the laws of nature seem to be invariant under the symmetry transformation of spacetimealthough it is model dependent 2 . A number of high-precision CPT and Lorentz invariance tests-using a co-magnetometer, a torsion pendulum and a maser, among others-have been performed 3 , but only a few direct high-precision CPT tests that compare the fundamental properties of matter and antimatter are available [4][5][6][7][8] . Here we report high-precision cyclotron frequency comparisons of a single antiproton and a negatively charged hydrogen ion (H 2 ) carried out in a Penning trap system. From 13,000 frequency measurements we compare the charge-to-mass ratio for the antiproton (q=m) p to that for the proton q=m ð Þ p and obtain q=m ð{12 . The measurements were performed at cyclotron frequencies of 29.6 megahertz, so our result shows that the CPT theorem holds at the atto-electronvolt scale. Our precision of 69 parts per trillion exceeds the energy resolution of previous antiproton-toproton mass comparisons 7,9 as well as the respective figure of merit of the standard model extension 10 by a factor of four. In addition, we give a limit on sidereal variations in the measured ratio of ,720 parts per trillion. By following the arguments of ref. 11, our result can be interpreted as a stringent test of the weak equivalence principle of general relativity using baryonic antimatter, and it sets a new limit on the gravitational anomaly parameter of a g {1 , 8.7 3 10 27 . The standard model is the theory that describes particles and their fundamental interactions, although without taking into account gravitation. However, this model is known to be incomplete, which has inspired searches for physics beyond the standard model, such as tests of CPT invariance that compare the fundamental properties of matterto-antimatter equivalents at the lowest energies and with the greatest precision [12][13][14][15] . For leptons, for example, the magnetic anomalies of electron and positron were compared with a fractional uncertainty of about 2 parts per billion 4 , and by applying similar techniques to protons and antiprotons, the resulting g-factor (a proportionality constant which links the spin of a particle to its magnetic moment) comparison reached a precision of 4.4 parts per million 8 . We are planning to improve this measurement by at least a factor of a thousand 16,17 . In this context, we recently reported the most precise and first direct high-precision measurement of the proton magnetic moment, with a fractional precision of 3.3 parts per billion 18 . Complementary to these efforts, spectroscopic comparisons of hydrogen and antihydrogen are underway; recent progress has been...

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Precise comparisons of the fundamental properties of matterantimatter conjugates provide sensitive tests of charge-parity-time (CPT) invariance 1 , which is an important symmetry that rests on basic assumptions of the standard model of particle physics. Experiments on mesons 2 , leptons 3,4 and baryons 5,6 have compared different properties of matter-antimatter conjugates with fractional uncertainties at the parts-per-billion level or better. One specific quantity, however, has so far only been known to a fractional uncertainty at the parts-per-million level 7,8 : the magnetic moment of the antiproton, μ p . The extraordinary difficulty in measuring μ p with high precision is caused by its intrinsic smallness; for example, it is 660 times smaller than the magnetic moment of the positron 3 . Here we report a high-precision measurement of μ p in units of the nuclear magneton μ N with a fractional precision of 1.5 parts per billion (68% confidence level). We use a two-particle spectroscopy method in an advanced cryogenic multi-Penning trap system. Our result μ p = −2.7928473441(42)μ N (where the number in parentheses represents the 68% confidence interval on the last digits of the value) improves the precision of the previous best μ p measurement 8 by a factor of approximately 350. The measured value is consistent with the proton magnetic moment 9 , μ p = 2.792847350(9)μ N , and is in agreement with CPT invariance. Consequently, this measurement constrains the magnitude of certain CPT-violating effects 10 to below 1.8 × 10 −24 gigaelectronvolts, and a possible splitting of the protonantiproton magnetic moments by CPT-odd dimension-five interactions to below 6 × 10 −12 Bohr magnetons 11 .Within the physics programme at the Antiproton Decelerator of CERN, the properties of protons and antiprotons 5,6 , antiprotons and electrons 12 , and hydrogen 13 and antihydrogen 14,15 are compared with high precision. Such experiments, including those described here, provide stringent tests of CPT invariance. Our presented antiproton magnetic moment measurement reaches a fractional precision of 1.5 parts per billion (p.p.b.) at 68% confidence level, enabled by our new measurement scheme. Compared to the double-Penning trap technique 16 used in the measurement of the proton magnetic moment 9 , this new method eliminates the need for cyclotron cooling in each measurement cycle and increases the sampling rate.Our technique uses a hot cyclotron antiproton for measurements of the cyclotron frequency ν c , and a cold Larmor antiproton to determine the Larmor frequency ν L . By evaluating the ratio of the frequencies measured in the same magnetic field, the magnetic moment of the antiproton (in units of the nuclear magneton, the g-factor) ν ν μ μN is obtained. With this new technique we have improved the precision of the previous best antiproton magnetic moment measurement 8 by a factor of approximately 350 (Fig. 1a).Our experiment 17 is located in the Antiproton Decelerator facility, which provides bunches of 30 million antiprotons at a...

Precise knowledge of the fundamental properties of the proton is essential for our understanding of atomic structure as well as for precise tests of fundamental symmetries. We report on a direct high-precision measurement of the magnetic moment μ of the proton in units of the nuclear magneton μ The result, μ = 2.79284734462 (±0.00000000082) μ, has a fractional precision of 0.3 parts per billion, improves the previous best measurement by a factor of 11, and is consistent with the currently accepted value. This was achieved with the use of an optimized double-Penning trap technique. Provided a similar measurement of the antiproton magnetic moment can be performed, this result will enable a test of the fundamental symmetry between matter and antimatter in the baryonic sector at the 10 level.

Abstract. The Baryon Antibaryon Symmetry Experiment (BASE) aims at performing a stringent test of the combined charge parity and time reversal (CPT) symmetry by comparing the magnetic moments of the proton and the antiproton with high precision. Using single particles in a Penning trap, the proton/antiproton g-factors, i.e. the magnetic moment in units of the nuclear magneton, are determined by measuring the respective ratio of the spin-precession frequency to the cyclotron frequency. The spin precession frequency is measured by non-destructive detection of spin quantum transitions using the continuous Stern-Gerlach effect, and the cyclotron frequency is determined from the particle's motional eigenfrequencies in the Penning trap using the invariance theorem. By application of the double Penningtrap method we expect that in our measurements a fractional precision of δg/g 10

The zero-order dependence of the rate of chlorination of p-cresol by chloramine-T on the concentration of the phenol has previously been attributed to the formation of hypochlorous acid from the chloro-sulphonamide as being the rate-determining step. Evidence is presented to show that the reaction actually proceeds through dichloramine-T and that the rate of formation of this species constitutes the limiting step.

The drug/metabolite transporter (DMT) superfamily is a large group of membrane transporters ubiquitously found in eukaryotes, bacteria and archaea, and includes exporters for a remarkably wide range of substrates, such as toxic compounds and metabolites. YddG is a bacterial DMT protein that expels aromatic amino acids and exogenous toxic compounds, thereby contributing to cellular homeostasis. Here we present structural and functional analyses of YddG. Using liposome-based analyses, we show that Escherichia coli and Starkeya novella YddG export various amino acids. The crystal structure of S. novella YddG at 2.4 Å resolution reveals a new membrane transporter topology, with ten transmembrane segments in an outward-facing state. The overall structure is basket-shaped, with a large substrate-binding cavity at the centre of the molecule, and is composed of inverted structural repeats related by two-fold pseudo-symmetry. On the basis of this intramolecular symmetry, we propose a structural model for the inward-facing state and a mechanism of the conformational change for substrate transport, which we confirmed by biochemical analyses. These findings provide a structural basis for the mechanism of transport of DMT superfamily proteins.