Practical Spectrophotometric Assay for the \u3cem\u3edapE\u3c/em\u3e-Encoded \u3cem\u3eN\u3c/em\u3e-Succinyl-L,L-Diaminopimelic Acid Desuccinylase, a Potential Antibiotic Target

A new enzymatic assay for the bacterial enzyme succinyl-diaminopimelate desuccinylase (DapE, E.C. 3.5.1.18) is described. This assay employs N6-methyl-N2-succinyl-L,L-diaminopimelic acid (N6-methyl-L,L-SDAP) as the substrate with ninhydrin used to detect cleavage of the amide bond of the modified substrate, wherein N6-methylation enables selective detection of the primary amine enzymatic product. Molecular modeling supported preparation of the mono-N6-methylated-L,L-SDAP as an alternate substrate for the assay, given binding in the active site of DapE predicted to be comparable to the endogenous substrate. The alternate substrate for the assay, N6-methyl-L,L-SDAP, was synthesized from the tert-butyl ester of Boc-L-glutamic acid employing a Horner-Wadsworth-Emmons olefination followed by an enantioselective reduction employing Rh(I)(COD)(S,S)-Et-DuPHOS as the chiral catalyst. Validation of the new ninhydrin assay was demonstrated with known inhibitors of DapE from Haemophilus influenza (HiDapE) including captopril (IC50 = 3.4 [± 0.2] μM, 3-mercaptobenzoic acid (IC50 = 21.8 [±2.2] μM, phenylboronic acid (IC50 = 316 [± 23.6] μM, and 2-thiopheneboronic acid (IC50 = 111 [± 16] μM. Based on these data, this assay is simple and robust, and should be amenable to high-throughput screening, which is an important step forward as it opens the door to medicinal chemistry efforts toward the discovery of DapE inhibitors that can function as a new class of antibiotics

Limitations of squeezing due to collisional decoherence in Bose-Einstein condensates

We study the limitations for entanglement due to collisional decoherence in a Bose-Einstein condensate. Specifically we consider relative number squeezing between photons and atoms coupled out from a homogeneous condensate. We study the decay of excited quasiparticle modes due to collisions, in condensates of atoms with one or two internal degrees of freedom. The time evolution of these modes is determined in the linear response approximation to the deviation from equilibrium. We use Heisenberg-Langevin equations to derive equations of motion for the densities and higher correlation functions which determine the squeezing. In this way we can show that decoherence due to quasiparticle interactions imposes an important limit on the degree of number squeezing which may be achieved. Our results are also relevant for the determination of decoherence times in other experiments based on entanglement, e.g. the slowing and stopping of light in condensed atomic gases using dark states.Comment: 16 pages RevTeX, 3 figure

Energies and damping rates of elementary excitations in spin-1 Bose-Einstein condensed gases

Finite temperature Green's function technique is used to calculate the energies and damping rates of elementary excitations of the homogeneous, dilute, spin-1 Bose gases below the Bose-Einstein condensation temperature both in the density and spin channels. For this purpose the self-consistent dynamical Hartree-Fock model is formulated, which takes into account the direct and exchange processes on equal footing by summing up certain classes of Feynman diagrams. The model is shown to fulfil the Goldstone theorem and to exhibit the hybridization of one-particle and collective excitations correctly. The results are applied to the gases of ^{23}Na and ^{87}Rb atoms.Comment: 26 pages, 21 figures. Added 2 new figures, detailed discussio

Cyclobutanone Inhibitor of Cobalt-Functionalized Metallo-γ-Lactonase AiiA with Cyclobutanone Ring Opening in the Active Site

An α-amido cyclobutanone possessing a C10 hydrocarbon tail was designed as a potential transition-state mimetic for the quorum-quenching metallo-γ-lactonase autoinducer inactivator A (AiiA) with the support of in-house modeling techniques and found to be a competitive inhibitor of dicobalt(II) AiiA with an inhibition constant of Ki = 0.007 ± 0.002 mM. The catalytic mechanism of AiiA was further explored using our product-based transition-state modeling (PBTSM) computational approach, providing substrate-intermediate models arising during enzyme turnover and further insight into substrate–enzyme interactions governing native substrate catalysis. These interactions were targeted in the docking of cyclobutanone hydrates into the active site of AiiA. The X-ray crystal structure of dicobalt(II) AiiA cocrystallized with this cyclobutanone inhibitor unexpectedly revealed an N-(2-oxocyclobutyl)decanamide ring-opened acyclic product bound to the enzyme active site (PDB 7L5F). The C10 alkyl chain and its interaction with the hydrophobic phenylalanine clamp region of AiiA adjacent to the active site enabled atomic placement of the ligand atoms, including the C10 alkyl chain. A mechanistic hypothesis for the ring opening is proposed involving a radical-mediated process

Quadrupole collective modes in trapped finite-temperature Bose-Einstein condensates

Finite temperature simulations are used to study quadrupole excitations of a trapped Bose-Einstein condensate. We focus specifically on the m=0 mode, where a long-standing theoretical problem has been to account for an anomalous variation of the mode frequency with temperature. We explain this behavior in terms of the excitation of two separate modes, corresponding to coupled motion of the condensate and thermal cloud. The relative amplitudes of the modes depends sensitively on the temperature and on the frequency of the harmonic drive used to excite them. Good agreement with experiment is found for appropriate drive frequencies.Comment: 4 pages, 3 figure

Equilibrium and dynamical properties of two dimensional self-gravitating systems

A system of N classical particles in a 2D periodic cell interacting via long-range attractive potential is studied. For low energy density $U$ a collapsed phase is identified, while in the high energy limit the particles are homogeneously distributed. A phase transition from the collapsed to the homogeneous state occurs at critical energy U_c. A theoretical analysis within the canonical ensemble identifies such a transition as first order. But microcanonical simulations reveal a negative specific heat regime near $U_c$. The dynamical behaviour of the system is affected by this transition : below U_c anomalous diffusion is observed, while for U > U_c the motion of the particles is almost ballistic. In the collapsed phase, finite $N$-effects act like a noise source of variance O(1/N), that restores normal diffusion on a time scale diverging with N. As a consequence, the asymptotic diffusion coefficient will also diverge algebraically with N and superdiffusion will be observable at any time in the limit N \to \infty. A Lyapunov analysis reveals that for U > U_c the maximal exponent \lambda decreases proportionally to N^{-1/3} and vanishes in the mean-field limit. For sufficiently small energy, in spite of a clear non ergodicity of the system, a common scaling law \lambda \propto U^{1/2} is observed for any initial conditions.Comment: 17 pages, Revtex - 15 PS Figs - Subimitted to Physical Review E - Two column version with included figures : less paper waste

Thermodynamics of a Trapped Bose-Fermi Mixture

By using the Hartree-Fock-Bogoliubov equations within the Popov approximation, we investigate the thermodynamic properties of a dilute binary Bose-Fermi mixture confined in an isotropic harmonic trap. For mixtures with an attractive Bose-Fermi interaction we find a sizable enhancement of the condensate fraction and of the critical temperature of Bose-Einstein condensation with respect to the predictions for a pure interacting Bose gas. Conversely, the influence of the repulsive Bose-Fermi interaction is less pronounced. The possible relevance of our results in current experiments on trapped $^{87}{\rm Rb}-^{40}${\rm K} mixtures is discussed.Comment: 5 pages + 4 figures; minor changes, final version to appear in Phys. Rev. A; the extension work on the finite-temperature low-lying excitations can be found in cond-mat/030763

Landau damping in trapped Bose-condensed gases

We study Landau damping in dilute Bose-Einstein condensed gases in both spherical and prolate ellipsoidal harmonic traps. We solve the Bogoliubov equations for the mode spectrum in both of these cases, and calculate the damping by summing over transitions between excited quasiparticle states. The results for the spherical case are compared to those obtained in the Hartree-Fock approximation, where the excitations take on a single-particle character, and excellent agreement between the two approaches is found. We have also taken the semiclassical limit of the Hartree-Fock approximation and obtain a novel expression for the Landau damping rate involving the time dependent self-diffusion function of the thermal cloud. As a final approach, we study the decay of a condensate mode by making use of dynamical simulations in which both the condensate and thermal cloud are evolved explicitly as a function of time. A detailed comparison of all these methods over a wide range of sample sizes and trap geometries is presented.Comment: 18 pages, 13 figures, submitted to the New Journal of Physics focus issue on Quantum Gase