285 research outputs found
Structural diversity in the AdoMet radical enzyme superfamily
AdoMet radical enzymes are involved in processes such as cofactor biosynthesis, anaerobic metabolism, and natural product biosynthesis. These enzymes utilize the reductive cleavage of S-adenosylmethionine (AdoMet) to afford l-methionine and a transient 5′-deoxyadenosyl radical, which subsequently generates a substrate radical species. By harnessing radical reactivity, the AdoMet radical enzyme superfamily is responsible for an incredible diversity of chemical transformations. Structural analysis reveals that family members adopt a full or partial Triose-phosphate Isomerase Mutase (TIM) barrel protein fold, containing core motifs responsible for binding a catalytic [4Fe–4S] cluster and AdoMet. Here we evaluate over twenty structures of AdoMet radical enzymes and classify them into two categories: ‘traditional’ and ‘ThiC-like’ (named for the structure of 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase (ThiC)). In light of new structural data, we reexamine the ‘traditional’ structural motifs responsible for binding the [4Fe–4S] cluster and AdoMet, and compare and contrast these motifs with the ThiC case. We also review how structural data combine with biochemical, spectroscopic, and computational data to help us understand key features of this enzyme superfamily, such as the energetics, the triggering, and the molecular mechanisms of AdoMet reductive cleavage. This article is part of a Special Issue entitled: Radical SAM Enzymes and Radical Enzymology.Wellcome Trust (London, England) (091162/Z/10/Z)National Science Foundation (U.S.) (NSF Grant MCB-0543833)Howard Hughes Medical Institute (Investigator
Consistent Anisotropic Repulsions for Simple Molecules
We extract atom-atom potentials from the effective spherical potentials that
suc cessfully model Hugoniot experiments on molecular fluids, e.g., and
. In the case of the resulting potentials compare very well with the
atom-atom potentials used in studies of solid-state propertie s, while for
they are considerably softer at short distances. Ground state (T=0K) and
room temperatu re calculations performed with the new potential resolve
the previous discrepancy between experimental and theoretical results.Comment: RevTeX, 5 figure
Proteolytic processing of human cytomegalovirus glycoprotein B (gpUL55) is mediatedby the human endoprotease furin
AbstractInhibition of endoproteolytic cleavage of glycoprotein B (gB; gpUL55) of human cytomegalovirus was achieved by treatmentof infected fibroblasts with decanoyl peptidyl chloromethyl ketone (decRVKR-CMK), which inhibits the action of cellular subtilisin-like endoproteases with the amino acid recognition motif R × K/R R. Uncleaved gB precusor molecules of 160 kDa that were accumulated were endoglycosidase H resistant, suggesting that correct cellular transport occurred in the presence of the drug. The inhibitor also prevented endoproteolytic gB processing in CV-1 cells infected with a recombinant vaccinia virus-gB construct (VVgB). Evidence for direct involvement of the ubiquitous subtilisin-like endoprotease furin in gB cleavage was obtained from the observation that coinfection of CV-1 cells with WgB and a recombinant vaccinia-human furin construct reestablished endoproteolytic activity which was normally absent late after infection with WgB alone
Wigner Trajectory Characteristics in Phase Space and Field Theory
Exact characteristic trajectories are specified for the time-propagating
Wigner phase-space distribution function. They are especially simple---indeed,
classical---for the quantized simple harmonic oscillator, which serves as the
underpinning of the field theoretic Wigner functional formulation introduced.
Scalar field theory is thus reformulated in terms of distributions in field
phase space. Applications to duality transformations in field theory are
discussed.Comment: 9 pages, LaTex2
CR1 acute myeloid leukemia and HLA-identical allogeneic transplantation (ASCT) prepared with reduced intensity regimen (RIC): leukemia control requires adequate pre graft chemotherapy and post graft GVHD
Turing instabilities in a mathematical model for signaling networks
GTPase molecules are important regulators in cells that continuously run
through an activation/deactivation and membrane-attachment/membrane-detachment
cycle. Activated GTPase is able to localize in parts of the membranes and to
induce cell polarity. As feedback loops contribute to the GTPase cycle and as
the coupling between membrane-bound and cytoplasmic processes introduces
different diffusion coefficients a Turing mechanism is a natural candidate for
this symmetry breaking. We formulate a mathematical model that couples a
reaction-diffusion system in the inner volume to a reaction-diffusion system on
the membrane via a flux condition and an attachment/detachment law at the
membrane. We present a reduction to a simpler non-local reaction-diffusion
model and perform a stability analysis and numerical simulations for this
reduction. Our model in principle does support Turing instabilities but only if
the lateral diffusion of inactivated GTPase is much faster than the diffusion
of activated GTPase.Comment: 23 pages, 5 figures; The final publication is available at
http://www.springerlink.com http://dx.doi.org/10.1007/s00285-011-0495-
Cross-generational trans fat intake exacerbates UV radiation-induced damage in rat skin
AbstractWe evaluated the influence of dietary fats on ultraviolet radiation (UVR)-induced oxidative damage in skin of rats. Animals from two consecutive generations born of dams supplemented with fats during pregnancy and breastfeeding were maintained in the same supplementation: soybean-oil (SO, rich in n-6 FA, control group), fish-oil (FO, rich in n-3 FA) or hydrogenated-vegetable-fat (HVF, rich in TFA). At 90days of age, half the animals from the 2nd generation were exposed to UVR (0.25J/cm2) 3×/week for 12weeks. The FO group presented higher incorporation of n-3 FA in dorsal skin, while the HVF group incorporated TFA. Biochemical changes per se were observed in skin of the HVF group: greater generation of reactive oxygen species (ROS), lower mitochondrial integrity and increased Na+K+-ATPase activity. UVR exposure increased skin wrinkles scores and ROS generation and decreased mitochondrial integrity and reduced-glutathione levels in the HVF group. In FO, UVR exposure was associated with smaller skin thickness and reduced levels of protein–carbonyl, together with increased catalase activity and preserved Na+K+-ATPase function. In conclusion, while FO may be protective, trans fat may be harmful to skin health by making it more vulnerable to UVR injury and thus more prone to develop photoaging and skin cancer
Features of Time-independent Wigner Functions
The Wigner phase-space distribution function provides the basis for Moyal's
deformation quantization alternative to the more conventional Hilbert space and
path integral quantizations. General features of time-independent Wigner
functions are explored here, including the functional ("star") eigenvalue
equations they satisfy; their projective orthogonality spectral properties;
their Darboux ("supersymmetric") isospectral potential recursions; and their
canonical transformations. These features are illustrated explicitly through
simple solvable potentials: the harmonic oscillator, the linear potential, the
Poeschl-Teller potential, and the Liouville potential.Comment: 18 pages, plain LaTex, References supplemente
- …