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281.
Domenica Farci Matthew W. Bowler Joanna Kirkpatrick Sean McSweeney Enzo Tramontano Dario Piano 《生物化学与生物物理学报:生物膜》2014
We have analyzed the cell wall of the radio-resistant bacterium Deinococcus radiodurans. Unexpectedly, the bacterial envelope appears to be organized in different complexes of high molecular weight. Each complex is composed of several proteins, most of which are coded by genes of unknown function and the majority are constituents of the inner/outer membrane system. One of the most abundant complexes is constituted by the gene DR_0774. This protein is a type of secretin which is a known subunit of the homo-oligomeric channel that represents the main bulk of the type IV piliation family. Finally, a minor component of the pink envelope consists of several inner-membrane proteins. The implications of these findings are discussed. 相似文献
282.
Adwait Anand Godbole Wareed Ahmed Rajeshwari Subray Bhat Erin K. Bradley Sean Ekins Valakunja Nagaraja 《Biochemical and biophysical research communications》2014
m-AMSA, an established inhibitor of eukaryotic type II topoisomerases, exerts its cidal effect by binding to the enzyme–DNA complex thus inhibiting the DNA religation step. The molecule and its analogues have been successfully used as chemotherapeutic agents against different forms of cancer. After virtual screening using a homology model of the Mycobacterium tuberculosis topoisomerase I, we identified m-AMSA as a high scoring hit. We demonstrate that m-AMSA can inhibit the DNA relaxation activity of topoisomerase I from M. tuberculosis and Mycobacterium smegmatis. In a whole cell assay, m-AMSA inhibited the growth of both the mycobacteria. 相似文献
283.
Sarunya Sujaritpong Keith Dear Martin Cope Sean Walsh Tord Kjellstrom 《International journal of biometeorology》2014,58(2):149-160
Climate change has been predicted to affect future air quality, with inevitable consequences for health. Quantifying the health effects of air pollution under a changing climate is crucial to provide evidence for actions to safeguard future populations. In this paper, we review published methods for quantifying health impacts to identify optimal approaches and ways in which existing challenges facing this line of research can be addressed. Most studies have employed a simplified methodology, while only a few have reported sensitivity analyses to assess sources of uncertainty. The limited investigations that do exist suggest that examining the health risk estimates should particularly take into account the uncertainty associated with future air pollution emissions scenarios, concentration-response functions, and future population growth and age structures. Knowledge gaps identified for future research include future health impacts from extreme air pollution events, interactions between temperature and air pollution effects on public health under a changing climate, and how population adaptation and behavioural changes in a warmer climate may modify exposure to air pollution and health consequences. 相似文献
284.
Meng-Hsin Phoebe Lee Sean M. Caffrey Johanna K. Voordouw Gerrit Voordouw 《Applied microbiology and biotechnology》2010,87(3):1109-1118
Although sulfate-reducing bacteria (SRB), such as Desulfovibrio vulgaris Hildenborough (DvH) are often eradicated in oil and gas operations with biocides, such as glutaraldehyde (Glut), tetrakis
(hydroxymethyl) phosphonium sulfate (THPS), and benzalkonium chloride (BAC), their response to these agents is not well known.
Whole genome microarrays of D. vulgaris treated with biocides well below the minimum inhibitory concentration showed that 256, 96, and 198 genes were responsive
to Glut, THPS, and BAC, respectively, and that these three commonly used biocides affect the physiology of the cell quite
differently. Glut induces expression of genes required to degrade or refold proteins inactivated by either chemical modification
or heat shock, whereas BAC appears to target ribosomal structure. THPS appears to primarily affect energy metabolism of SRB.
Mutants constructed for genes strongly up-regulated by Glut, were killed by Glut to a similar degree as the wild type. Hence,
it is difficult to achieve increased sensitivity to this biocide by single gene mutations, because Glut affects so many targets.
Our results increase understanding of the biocide's mode of action, allowing a more intelligent combination of mechanistically
different agents. This can reduce stress on budgets for chemicals and on the environment. 相似文献
285.
Tatiana P. Soares da Costa Andrew C. Muscroft-Taylor Renwick C.J. Dobson Sean R.A. Devenish Geoffrey B. Jameson Juliet A. Gerrard 《Biochimie》2010
Dihydrodipicolinate synthase (DHDPS, E.C. 4.2.1.52), a validated antibiotic target, catalyses the first committed step in the lysine biosynthetic pathway: the condensation reaction between (S)-aspartate β-semialdehyde [(S)-ASA] and pyruvate via the formation of a Schiff base intermediate between pyruvate and the absolutely conserved active-site lysine. Escherichia coli DHDPS mutants K161A and K161R of the active-site lysine were characterised for the first time. Unexpectedly, the mutant enzymes were still catalytically active, albeit with a significant decrease in activity. The kcat values for DHDPS-K161A and DHDPS-K161R were 0.06 ± 0.02 s−1 and 0.16 ± 0.06 s−1 respectively, compared to 45 ± 3 s−1 for the wild-type enzyme. Remarkably, the KM values for pyruvate increased by only 3-fold for DHDPS-K161A and DHDPS-K161R (0.45 ± 0.04 mM and 0.57 ± 0.06 mM, compared to 0.15 ± 0.01 mM for the wild-type DHDPS), while the KM values for (S)-ASA remained the same for DHDPS-K161R (0.12 ± 0.01 mM) and increased by only 2-fold for DHDPS-K161A (0.23 ± 0.02 mM) and the Ki for lysine was unchanged. The X-ray crystal structures of DHDPS-K161A and DHDPS-K161R were solved at resolutions of 2.0 and 2.1 Å respectively and showed no changes in their secondary or tertiary structures when compared to the wild-type structure. The crystal structure of DHDPS-K161A with pyruvate bound at the active site was solved at a resolution of 2.3 Å and revealed a defined binding pocket for pyruvate that is thus not dependent upon lysine 161. Taken together with ITC and NMR data, it is concluded that although lysine 161 is important in the wild-type DHDPS-catalysed reaction, it is not absolutely essential for catalysis. 相似文献
286.
287.
288.
Summary: Lipoic acid [(R)-5-(1,2-dithiolan-3-yl)pentanoic acid] is an enzyme cofactor required for intermediate metabolism in free-living cells. Lipoic acid was discovered nearly 60 years ago and was shown to be covalently attached to proteins in several multicomponent dehydrogenases. Cells can acquire lipoate (the deprotonated charge form of lipoic acid that dominates at physiological pH) through either scavenging or de novo synthesis. Microbial pathogens implement these basic lipoylation strategies with a surprising variety of adaptations which can affect pathogenesis and virulence. Similarly, lipoylated proteins are responsible for effects beyond their classical roles in catalysis. These include roles in oxidative defense, bacterial sporulation, and gene expression. This review surveys the role of lipoate metabolism in bacterial, fungal, and protozoan pathogens and how these organisms have employed this metabolism to adapt to niche environments. 相似文献
289.
MicroRNA-451 Regulates LKB1/AMPK Signaling and Allows Adaptation to Metabolic Stress in Glioma Cells
290.