A Conformational Switch in the Active Site of BT_2972, a Methyltransferase from an Antibiotic Resistant Pathogen B. thetaiotaomicron

Methylation is one of the most common biochemical reactions involved in cellular and metabolic functions and is catalysed by the action of methyltransferases. Bacteroides thetaiotaomicron is an antibiotic-resistant bacterium that confers resistance through methylation, and as yet, there is no report on the structure of methyltransferases from this bacterium. Here, we report the crystal structure of an AdoMet-dependent methyltransferase, BT_2972 and its complex with AdoMet and AdoHcy for B. thetaiotaomicron VPI-5482 strain along with isothermal titration calorimetric assessment of the binding affinities. Comparison of the apo and complexed BT_2972 structures reveals a significant conformational change between open and closed forms of the active site that presumably regulates the association with cofactors and may aid interaction with substrate. Together, our analysis suggests that BT_2972 is a small molecule methyltransferase and might catalyze two O-methylation reaction steps involved in the ubiquinone biosynthesis pathway

Crystal structures of PI3K-C2α PX domain indicate conformational change associated with ligand binding

<p>Abstract</p> <p>Background</p> <p>PX domains have specialized protein structures involved in binding of phosphoinositides (PIs). Through binding to the various PIs PX domains provide site-specific membrane signals to modulate the intracellular localisation and biological activity of effector proteins. Several crystal structures of these domains are now available from a variety of proteins. All PX domains contain a canonical core structure with main differences exhibited within the loop regions forming the phosphoinositide binding pockets. It is within these areas that the molecular basis for ligand specificity originates.</p> <p>Results</p> <p>We now report two new structures of PI3K-C2α PX domain that crystallised in a P3₁21 space group. The two structures, refined to 2.1 Å and 2.5 Å, exhibit significantly different conformations of the phosphoinositide-binding loops. Unexpectedly, in one of the structures, we have detected a putative-ligand trapped in the binding site during the process of protein purification and crystallisation.</p> <p>Conclusion</p> <p>The two structures reported here provide a more complete description of the phosphoinositide binding region compared to the previously reported 2.6 Å crystal structure of human PI3K-C2α PX where this region was highly disordered. The structures enabled us to further analyse PI specificity and to postulate that the observed conformational change could be related to ligand-binding.</p

Retired A Stars and Their Companions: Exoplanets Orbiting Three Intermediate-Mass Subgiants

We report precision Doppler measurements of three intermediate-mass subgiants from Lick and Keck Observatories. All three stars show variability in their radial velocities consistent with planet-mass companions in Keplerian orbits. We find a planet with a minimum mass of 2.5 Mjup in a 351.5 day orbit around HD 192699, a planet with a minimum mass of 2.0 Mjup in a 341.1 day orbit around HD 210702, and a planet with a minimum mass of 0.61 Mjup in a 297.3 day orbit around HD 175541. Stellar mass estimates from evolutionary models indicate that all of these stars were formerly A-type dwarfs with masses ranging from 1.65 to 1.85 Msun. These three long-period planets would not have been detectable during their stars' main-sequence phases due to the large rotational velocities and stellar jitter exhibited by early-type dwarfs. There are now 9 "retired" (evolved) A-type stars (Mstar > 1.6 Msun) with known planets. All 9 planets orbit at distances a \geq 0.78 AU, which is significantly different than the semimajor axis distribution of planets around lower-mass stars. We examine the possibility that the observed lack of close-in planets is due to engulfment by their expanding host stars, but we find that this explanation is inadequate given the relatively small stellar radii of K giants (Rstar < 32 Rsun = 0.15 AU) and subgiants (Rstar < 7 Rsun = 0.03 AU). Instead, we conclude that planets around intermediate-mass stars reside preferentially beyond ~0.8 AU, which may be a reflection of different formation and migration histories of planets around A-type stars.Comment: 31 pages, 9 figures, 6 tables, ApJ accepted, corrected minor typo

Nonstomatal limitations are responsible for drought-induced photosynthetic inhibition in four C4 grasses

Here, the contribution of stomatal and nonstomatal factors to photosynthetic inhibition under water stress in four tropical C(4) grasses was investigated (Panicum coloratum, Bothriochloa bladhii, Cenchrus ciliaris and Astrebla lappacea ). Plants were grown in well watered soil, and then the effects of soil drying were measured on leaf gas exchange, chlorophyll a fluorescence and water relations. During the drying cycle, leaf water potential (Psi(leaf)) and relative water content (RWC) decreased from c. -0.4 to -2.8 MPa and 100-40%, respectively. The CO(2) assimilation rates (A) and quantum yield of PSII (Phi(PSII)) of all four grasses decreased rapidly with declining RWC. High CO(2) concentration (2500 mul l(-1)) had no effect on A or Phi(PSII) at any stage of the drying cycle. Electron transport capacity and dark respiration rates were unaltered by drought. The CO(2) compensation concentrations of P. coloratum and C. ciliaris rose sharply when leaf RWC fell below 70%. In P. coloratum, 5% CO(2) did not prevent the decline of O(2) evolution rates under water stress. We conclude that inhibition of photosynthesis in the four C(4) grasses under water stress is dependent mainly on biochemical limitations

Anaplastic Lymphoma Kinase Spares Organ Growth during Nutrient Restriction in Drosophila

SummaryDeveloping animals survive periods of starvation by protecting the growth of critical organs at the expense of other tissues. Here, we use Drosophila to explore the as yet unknown mechanisms regulating this privileged tissue growth. As in mammals, we observe in Drosophila that the CNS is more highly spared than other tissues during nutrient restriction (NR). We demonstrate that anaplastic lymphoma kinase (Alk) efficiently protects neural progenitor (neuroblast) growth against reductions in amino acids and insulin-like peptides during NR via two mechanisms. First, Alk suppresses the growth requirement for amino acid sensing via Slimfast/Rheb/TOR complex 1. And second, Alk, rather than insulin-like receptor, primarily activates PI3-kinase. Alk maintains PI3-kinase signaling during NR as its ligand, Jelly belly (Jeb), is constitutively expressed from a glial cell niche surrounding neuroblasts. Together, these findings identify a brain-sparing mechanism that shares some regulatory features with the starvation-resistant growth programs of mammalian tumors.PaperCli

Holocene sediment distribution on the inner continental shelf of northeastern South Carolina : implications for the regional sediment budget and long-term shoreline response

This paper is not subject to U.S. copyright. The definitive version was published in Continental Shelf Research 56 (2013): 56-70, doi:10.1016/j.csr.2013.02.004.High-resolution geophysical and sediment sampling surveys were conducted offshore of the Grand Strand, South Carolina to define the shallow geologic framework of the inner shelf. Results are used to identify and map Holocene sediment deposits, infer sediment transport pathways, and discuss implications for the regional coastal sediment budget. The thickest deposits of Holocene sediment observed on the inner shelf form shoal complexes composed of moderately sorted fine sand, which are primarily located offshore of modern tidal inlets. These shoal deposits contain ∼67 M m3 of sediment, approximately 96% of Holocene sediment stored on the inner shelf. Due to the lack of any significant modern fluvial input of sand to the region, the Holocene deposits are likely derived from reworking of relict Pleistocene and older inner-shelf deposits during the Holocene marine transgression. The Holocene sediments are concentrated in the southern part of the study area, due to a combination of ancestral drainage patterns, a regional shift in sediment supply from the northeast to the southwest in the late Pleistocene, and proximity to modern inlet systems. Where sediment is limited, only small, low relief ridges have formed and Pleistocene and older deposits are exposed on the seafloor. The low-relief ridges are likely the result of a thin, mobile veneer of sediment being transported across an irregular, erosional surface formed during the last transgression. Sediment textural trends and seafloor morphology indicate a long-term net transport of sediment to the southwest. This is supported by oceanographic studies that suggest the long-term sediment transport direction is controlled by the frequency and intensity of storms that pass through the region, where low pressure systems yield net along-shore flow to the southwest and a weak onshore component. Current sediment budget estimates for the Grand Strand yield a deficit for the region. Volume calculations of Holocene deposits on the inner shelf suggest that there is sufficient sediment to balance the sediment budget and provide a source of sediment to the shoreline. Although the processes controlling cross-shelf sediment transport are not fully understood, in sediment-limited environments such as the Grand Strand, erosion of the inner shelf likely contributes significant sediment to the beach system