Gating mechanism of elongating β-ketoacyl-ACP synthases.

Carbon-carbon bond forming reactions are essential transformations in natural product biosynthesis. During de novo fatty acid and polyketide biosynthesis, β-ketoacyl-acyl carrier protein (ACP) synthases (KS), catalyze this process via a decarboxylative Claisen-like condensation reaction. KSs must recognize multiple chemically distinct ACPs and choreograph a ping-pong mechanism, often in an iterative fashion. Here, we report crystal structures of substrate mimetic bearing ACPs in complex with the elongating KSs from Escherichia coli, FabF and FabB, in order to better understand the stereochemical features governing substrate discrimination by KSs. Complemented by molecular dynamics (MD) simulations and mutagenesis studies, these structures reveal conformational states accessed during KS catalysis. These data taken together support a gating mechanism that regulates acyl-ACP binding and substrate delivery to the KS active site. Two active site loops undergo large conformational excursions during this dynamic gating mechanism and are likely evolutionarily conserved features in elongating KSs

Concerning the Wave equation on Asymptotically Euclidean Manifolds

We obtain KSS, Strichartz and certain weighted Strichartz estimate for the wave equation on $(\R^d, \mathfrak{g})$, $d \geq 3$, when metric $\mathfrak{g}$ is non-trapping and approaches the Euclidean metric like $x ^{- \rho}$ with $\rho>0$. Using the KSS estimate, we prove almost global existence for quadratically semilinear wave equations with small initial data for $\rho> 1$ and $d=3$. Also, we establish the Strauss conjecture when the metric is radial with $\rho>0$ for $d= 3$.Comment: Final version. To appear in Journal d'Analyse Mathematiqu

Keplerian Squeezed States and Rydberg Wave Packets

We construct minimum-uncertainty solutions of the three-dimensional Schr\"odinger equation with a Coulomb potential. These wave packets are localized in radial and angular coordinates and are squeezed states in three dimensions. They move on elliptical keplerian trajectories and are appropriate for the description of the corresponding Rydberg wave packets, the production of which is the focus of current experimental effort. We extend our analysis to incorporate the effects of quantum defects in alkali-metal atoms, which are used in experiments.Comment: accepted for publication in Physical Review

Chain-end modifications and sequence arrangements of antimicrobial peptoids for mediating activity and nano-assembly

Poly(N-substituted glycine) “peptoids” are an interesting class of peptidomimics that can resist proteolysis and mimic naturally found antimicrobial peptides (AMPs), which exhibit wide spectrum activity against bacteria. This work investigates the possibility of modifying peptoid AMP mimics (AMPMs) with aliphatic lipid “tails” to generate “lipopeptoids” that can assemble into micellar nanostructures, and evaluates their antimicrobial activities. Two families of AMPMs with different distributions of hydrophobic and cationic residues were employed—one with a uniform repeating amphiphilicity, the other with a surfactant-like head-to-tail amphiphilicity. To further evaluate the interplay between self-assembly and activity, the lipopeptoids were variously modified at the AMPM chain ends with a diethylene glycol (EG2) and/or a cationic group (Nlys-Nlys dipeptoid) to adjust amphiphilicity and chain flexibility. Self-assembly was investigated by critical aggregation concentration (CAC) fluorescence assays and dynamic light scattering (DLS). The structure of a key species was also verified by small-angle X-ray scattering (SAXS) and cryo-electron microscopy (cryo-EM). To screen for antibacterial properties, we measured the minimum inhibitory concentrations (MIC) against S. aureus, E. coli, and P. aeruginosa. We found that certain combinations of lipid tail and AMPM sequences exhibit increased antibacterial activity (i.e., decreased MICs). Perhaps counter-intuitively, we were particularly interested in increased MICs in combination with low CACs. Concealing antimicrobial interactions due to packing of AMPMs in nano-assemblies could pave the way to AMPMs that may be “inert” even if unintentionally released and prevent microbes from gaining resistance to the lipopeptoids. Overall, incorporation of EG2 significantly improved lipopeptoids packing while the hydrophobic tail length was found to have a major influence over the MIC. One particular sequence, which we named C15-EG2-(kss)4, exhibited a very low CAC of 34 μM (0.0075 wt.%) and a significantly increased MIC above values for the unmodified AMPM. With the sequence design trends uncovered from this study, future work will focus on discovering more species such as C15-EG2-(kss)4 and on investigating release mechanisms and the potency of the released lipopeptoids

The viscosity bound in string theory

The ratio of shear viscosity to entropy density $\eta/s$ of any material in nature has been conjectured to have a lower bound of $1/4\pi$, the famous KSS bound. We examine string theory models for evidence in favour of and against this conjecture. We show that in a broad class of models quantum corrections yield values of $\eta/s$ just above the KSS bound. However, incorporating matter fields in the fundamental representation typically leads to violations of this bound. We also outline a program to extend AdS/CFT methods to RHIC phenomenology.Comment: 4 pages, To appear in the conference proceedings for Quark Matter 2009, March 30 - April 4, Knoxville, Tennesse