40 research outputs found
Genome-wide association studies identify multiple genetic loci influencing eyebrow color variation in Europeans
Characterization of the N -Acetyl-α- d -glucosaminyl l -Malate Synthase and Deacetylase Functions for Bacillithiol Biosynthesis in Bacillus anthracis ,
Bacillithiol (Cys-GlcN-malate, BSH) has recently been identified as a novel low-molecular-weight thiol in Bacillus anthracis, Staphylococcus aureus, and several other Gram-positive bacteria lacking glutathione and mycothiol. We have now characterized the first two enzymes for the BSH biosynthetic pathway in B. anthracis, which combine to produce α-D-glucosaminyl L-malate (GlcN-malate) from UDP-GlcNAc and L-malate. The structure of the GlcNAc-malate intermediate has been determined, as have the kinetic parameters for the BaBshA glycosyltransferase (→GlcNAc-malate) and the BaBshB deacetylase (→GlcN-malate). BSH is one of only two natural products reported to contain a malyl glycoside, and the crystal structure of the BaBshA-UDP-malate ternary complex, determined in this work at 3.3 Å resolution, identifies several active-site interactions important for the specific recognition of L-malate, but not other α-hydroxyacids, as acceptor substrate. In sharp contrast to the structures reported for the GlcNAc—1-D-myo-inositol-3-phosphate synthase (MshA) apo and ternary complex forms, there is no major conformational change observed in the structures of the corresponding BaBshA forms. A mutant strain of B. anthracis deficient in the BshA glycosyltransferase fails to produce BSH, as predicted. This B. anthracis bshA locus (BA1558) has been identified in a transposon site hybridization study as required for growth, sporulation, or germination, suggesting that the biosynthesis of BSH could represent a target for development of novel antimicrobials with broad spectrum activity against Gram-positive pathogens like B. anthracis. The metabolites that function in thiol redox buffering and homeostasis in Bacillus are not well understood, and we present a composite picture based on this and other recent work
Genome-Wide Association Studies Identify Multiple Genetic Loci Influencing Eyebrow Color Variation in Europeans
All-sky search for gravitational-wave bursts in the second joint LIGO-Virgo run
We present results from a search for gravitational-wave bursts in the data
collected by the LIGO and Virgo detectors between July 7, 2009 and October 20,
2010: data are analyzed when at least two of the three LIGO-Virgo detectors are
in coincident operation, with a total observation time of 207 days. The
analysis searches for transients of duration < 1 s over the frequency band
64-5000 Hz, without other assumptions on the signal waveform, polarization,
direction or occurrence time. All identified events are consistent with the
expected accidental background. We set frequentist upper limits on the rate of
gravitational-wave bursts by combining this search with the previous LIGO-Virgo
search on the data collected between November 2005 and October 2007. The upper
limit on the rate of strong gravitational-wave bursts at the Earth is 1.3
events per year at 90% confidence. We also present upper limits on source rate
density per year and Mpc^3 for sample populations of standard-candle sources.
As in the previous joint run, typical sensitivities of the search in terms of
the root-sum-squared strain amplitude for these waveforms lie in the range 5
10^-22 Hz^-1/2 to 1 10^-20 Hz^-1/2. The combination of the two joint runs
entails the most sensitive all-sky search for generic gravitational-wave bursts
and synthesizes the results achieved by the initial generation of
interferometric detectors.Comment: 15 pages, 7 figures: data for plots and archived public version at
https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=70814&version=19, see
also the public announcement at
http://www.ligo.org/science/Publication-S6BurstAllSky
Characterization of the N-Acetyl-α-d-glucosaminyll-Malate Synthase and Deacetylase Functions for Bacillithiol Biosynthesis in Bacillus anthracis
Bacillithiol (Cys-GlcN-malate, BSH) has recently been identified as a novel low-molecular weight thiol in Bacillus anthracis, Staphylococcus aureus, and several other Gram-positive bacteria lacking glutathione and mycothiol. We have now characterized the first two enzymes for the BSH biosynthetic pathway in B. anthracis, which combine to produce a-d-glucosaminyl l-malate (GlcN-malate) from UDP-GlcNAc and l-malate. The structure of the GlcNAc-malate intermediate has been determined, as have the kinetic parameters for the BaBshA glycosyltransferase (?GlcNAc-malate) and the BaBshB deacetylase (?GlcN-malate). BSH is one of only two natural products reported to contain a malyl glycoside, and the crystal structure of the BaBshA-UDP-malate ternary complex, determined in this work at 3.3 Å resolution, identifies several active-site interactions important for the specific recognition of l-malate, but not other a-hydroxy acids, as the acceptor substrate. In sharp contrast to the structures reported for the GlcNAc-1-d-myo-inositol-3-phosphate synthase (MshA) apo and ternary complex forms, there is no major conformational change observed in the structures of the corresponding BaBshA forms. A mutant strain of B. anthracis deficient in the BshA glycosyltransferase fails to produce BSH, as predicted. This B. anthracis bshA locus (BA1558) has been identified in a transposon-site hybridization study as required for growth, sporulation, or germination [Day, W. A., Jr., Rasmussen, S. L., Carpenter, B. M., Peterson, S. N., and Friedlander, A. M. (2007) J. Bacteriol. 189, 3296-3301], suggesting that the biosynthesis of BSH could represent a target for the development of novel antimicrobials with broad-spectrum activity against Gram-positive pathogens like B. anthracis. The metabolites that function in thiol redox buffering and homeostasis in Bacillus are not well understood, and we present a composite picture based on this and other recent work