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1.
Claustre S Denier C Lakhdar-Ghazal F Lougare A Lopez C Chevalier N Michels PA Périé J Willson M 《Biochemistry》2002,41(32):10183-10193
This work deals with the phosphofructokinase enzyme (PFK) of the parasite Trypanosoma brucei. Inhibitors which are analogues of fructose-6-phosphate (F6P) derived from 2,5-anhydromannitol and therefore blocked in a closed conformation, both nonphosphorylated and phosphorylated, were designed. They provided information on this class of ATP-dependent PFK (structurally more similar to PPi-dependent PFKs revealing (i) an ordered mechanism, ATP binding first, inducing an essential conformational change to increase the affinity for F6P, and (ii) a rather hydrophobic environment at the ATP binding site. Nonphosphorylated mannitol derivatives bind at both the ATP and F6P binding sites, whereas the phosphorylated derivatives only bind at the ATP binding site. The inhibitors bearing an aromatic ring substituted at the meta position indicate a polar interaction with lysine 227, which is specific to T. brucei PFK and is replaced by a glycine in human PFK. This lysine can be irreversibly bound, leading to inhibition when an electrophilic carbon atom is beta to the meta position on the ring. This lysine was identified by site-directed mutagenesis. This first example of a specific irreversible inactivation of T. brucei PFK offers an opportunity to develop biologically active compounds against the sleeping sickness, the causative agent of which is the trypanosome. 相似文献
2.
Edmond M. Linossi Indu R. Chandrashekaran Tatiana B. Kolesnik James M. Murphy Andrew I. Webb Tracy A. Willson Lukasz Kedzierski Alex N. Bullock Jeffrey J. Babon Raymond S. Norton Nicos A. Nicola Sandra E. Nicholson 《PloS one》2013,8(8)
Suppressor of Cytokine Signaling (SOCS)5 is thought to act as a tumour suppressor through negative regulation of JAK/STAT and epidermal growth factor (EGF) signaling. However, the mechanism/s by which SOCS5 acts on these two distinct pathways is unclear. We show for the first time that SOCS5 can interact directly with JAK via a unique, conserved region in its N-terminus, which we have termed the JAK interaction region (JIR). Co-expression of SOCS5 was able to specifically reduce JAK1 and JAK2 (but not JAK3 or TYK2) autophosphorylation and this function required both the conserved JIR and additional sequences within the long SOCS5 N-terminal region. We further demonstrate that SOCS5 can directly inhibit JAK1 kinase activity, although its mechanism of action appears distinct from that of SOCS1 and SOCS3. In addition, we identify phosphoTyr317 in Shc-1 as a high-affinity substrate for the SOCS5-SH2 domain and suggest that SOCS5 may negatively regulate EGF and growth factor-driven Shc-1 signaling by binding to this site. These findings suggest that different domains in SOCS5 contribute to two distinct mechanisms for regulation of cytokine and growth factor signaling. 相似文献
3.
4.
Jacquelyn C. Guzy Brian J. Halstead Kelly M. Halloran Jessica A. Homyack John D. Willson 《Ecology and evolution》2021,11(24):17723
Timber harvesting can influence headwater streams by altering stream productivity, with cascading effects on the food web and predators within, including stream salamanders. Although studies have examined shifts in salamander occupancy or abundance following timber harvest, few examine sublethal effects such as changes in growth and demography. To examine the effect of upland harvesting on growth of the stream‐associated Ouachita dusky salamander (Desmognathus brimleyorum), we used capture–mark–recapture over three years at three headwater streams embedded in intensely managed pine forests in west‐central Arkansas. The pine stands surrounding two of the streams were harvested, with retention of a 14‐ and 21‐m‐wide forested stream buffer on each side of the stream, whereas the third stream was an unharvested control. At the two treatment sites, measurements of newly metamorphosed salamanders were on average 4.0 and 5.7 mm larger post‐harvest compared with pre‐harvest. We next assessed the influence of timber harvest on growth of post‐metamorphic salamanders with a hierarchical von Bertalanffy growth model that included an effect of harvest on growth rate. Using measurements from 839 individual D. brimleyorum recaptured between 1 and 6 times (total captures, n = 1229), we found growth rates to be 40% higher post‐harvest. Our study is among the first to examine responses of individual stream salamanders to timber harvesting, and we discuss mechanisms that may be responsible for observed shifts in growth. Our results suggest timber harvest that includes retention of a riparian buffer (i.e., streamside management zone) may have short‐term positive effects on juvenile stream salamander growth, potentially offsetting negative sublethal effects associated with harvest. 相似文献
5.
Reactions of the trichloromethylperoxy free radical (Cl3COO) with tryptophan, tryptophanyl-tyrosine and lysozyme 总被引:1,自引:0,他引:1
J E Packer J S Mahood R L Willson B S Wolfenden 《International journal of radiation biology and related studies in physics, chemistry, and medicine》1981,39(2):135-141
The trichloromethyl peroxy radical Cl3COO reacts with tryptophan, tryptophanyl-tyrosine and with lysozyme to form products whose overall absorption spectrum is different from those observed following the reaction of hydroxyl, bromide, thiocyanate or azide radicals. Two spectral components have been identified: a minor component attributed to the neutral tryptophanyl radical which can react with ascorbate and intramolecularly with tyrosine residues and a major component which does not undergo either of these reactions and is probably a radical adduct. 相似文献
6.
The anti-hen egg lysozyme monoclonal antibody HyHEL-5 and its complexes with various species-variant and mutant lysozymes have been the subject of considerable experimental and theoretical investigation. The affinity of HyHEL-5 for bobwhite quail lysozyme (BWQL) is over 1000-fold lower than its affinity for the original antigen, hen egg lysozyme (HEL). This difference is believed to arise almost entirely from the replacement in BWQL of the structural and energetic epitope residue Arg68 by lysine. In this study, the association and dissociation kinetics of BWQL with HyHEL-5 were investigated under a variety of conditions and compared with previous results for HEL. HyHEL-5-BWQL association follows a bimolecular mechanism and the dissociation of the antibody-antigen complex is a first-order process. Changes in ionic strength (from 27 to 500 mM) and pH (from 6.0 to 10.0) produced about a 2-fold change in the association and dissociation rates. The effect of viscosity modifiers on the association reaction was also studied. The large difference in the HEL and BWQL affinities for HyHEL-5 is essentially due to differences in the dissociation rate constant. 相似文献
7.
Riddle RR Gibbs PR Willson RC Benedik MJ 《Journal of industrial microbiology & biotechnology》2003,30(1):6-12
Biotechnological upgrading of fossil fuels is of increasing interest as remaining stocks of petroleum show increasing levels
of contaminants such as heavy metals, sulfur and nitrogen-containing heteroaromatic compounds. Carbazole is of particular
interest as a major petroleum component known to reduce refining yields through catalyst poisoning. In this study, the biotransformation
of carbazole was successfully demonstrated in a liquid two-phase system, when solubilized in either 1-methylnaphthalene or
in diesel fuel. The effects of solvent toxicity were investigated by expressing the carbazole-transformation genes from MB1332,
a rifampicin-resistant derivative of Pseudomonas sp. LD2, in a solvent-resistant heterologous host, P. putida Idaho [1]. This solvent-resistant strain successfully degraded carbazole solubilized in 1-methylnaphthalene and in the presence
of 10 vol% xylenes similar to the non-recombinant strain Pseudomonas sp. LD2. Identification of a suitable recombinant host, however, was essential for further investigations of partial pathway
transformations. Recombinant P. putida Idaho expressing only the initial dioxygenase enzymes transformed carbazole to an intermediate well retained in the oil phase.
Partial carbazole transformation converts carbazole to non-aromatic species; their effect is unknown on refinery catalyst
poisoning, but would allow almost complete retention of carbon content and fuel value.
Electronic Publication 相似文献
8.
CJ Cooksey 《Biotechnic & histochemistry》2014,89(5):384-387
The history, origin, identity, chemistry and uses of Congo red are described. Originally patented in 1884, Congo red soon found applications in dyeing cotton, as a pH indicator for chemists and as a biological stain. Unlike the majority of the 19th century synthetic dyes, it still is available commercially. 相似文献
9.
10.
Miao J Choi SE Seok SM Yang L Zuercher WJ Xu Y Willson TM Xu HE Kemper JK 《Molecular endocrinology (Baltimore, Md.)》2011,25(7):1159-1169