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991.
Erskine PT Knight MJ Ruaux A Mikolajek H Wong Fat Sang N Withers J Gill R Wood SP Wood M Fox GC Cooper JB 《Journal of molecular biology》2006,363(1):125-136
Burkoldheria pseudomallei is a Gram-negative bacterium that possesses a protein secretion system similar to those found in Salmonella and Shigella. Recent work has indicated that the protein encoded by the BipD gene of B. pseudomallei is an important secreted virulence factor. BipD is similar in sequence to IpaD from Shigella and SipD from Salmonella and is therefore likely to be a translocator protein in the type-III secretion system of B. pseudomallei. The crystal structure of BipD has been solved at a resolution of 2.1 A revealing the detailed tertiary fold of the molecule. The overall structure is appreciably extended and consists of a bundle of antiparallel alpha-helical segments with two small beta-sheet regions. The longest helices of the molecule form a four-helix bundle and most of the remaining secondary structure elements (three helices and two three-stranded beta-sheets) are formed by the region linking the last two helices of the four-helix bundle. The structure suggests that the biologically active form of the molecule may be a dimer formed by contacts involving the C-terminal alpha-helix, which is the most strongly conserved part of the protein. Comparison of the structure of BipD with immunological and other data for IpaD indicates that the C-terminal alpha-helix is also involved in contacts with other proteins that form the translocon. 相似文献
992.
Structural basis of substrate specificity in human glyoxylate reductase/hydroxypyruvate reductase 总被引:3,自引:0,他引:3
Human glyoxylate reductase/hydroxypyruvate reductase (GRHPR) is a D-2-hydroxy-acid dehydrogenase that plays a critical role in the removal of the metabolic by-product glyoxylate from within the liver. Deficiency of this enzyme is the underlying cause of primary hyperoxaluria type 2 (PH2) and leads to increased urinary oxalate levels, formation of kidney stones and renal failure. Here we describe the crystal structure of human GRHPR at 2.2 A resolution. There are four copies of GRHPR in the crystallographic asymmetric unit: in each homodimer, one subunit forms a ternary (enzyme+NADPH+reduced substrate) complex, and the other a binary (enzyme+NADPH) form. The spatial arrangement of the two enzyme domains is the same in binary and ternary forms. This first crystal structure of a true ternary complex of an enzyme from this family demonstrates the relationship of substrate and catalytic residues within the active site, confirming earlier proposals of the mode of substrate binding, stereospecificity and likely catalytic mechanism for these enzymes. GRHPR has an unusual substrate specificity, preferring glyoxylate and hydroxypyruvate, but not pyruvate. A tryptophan residue (Trp141) from the neighbouring subunit of the dimer is projected into the active site region and appears to contribute to the selectivity for hydroxypyruvate. This first crystal structure of a human GRHPR enzyme also explains the deleterious effects of naturally occurring missense mutations of this enzyme that lead to PH2. 相似文献
993.
Cadherin-like proteins have been identified as putative receptors for the Bacillus thuringiensis Cry1A proteins in Heliothis virescens and Manduca sexta. Immunohistochemistry showed the cadherin-like proteins are present in the insect midgut apical membrane, which is the target site of Cry toxins. This subcellular localization is distinct from that of classical cadherins, which are usually present in cell-cell junctions. Immunoreactivity of the cadherin-like protein in the insect midgut was enhanced by Cry1Ac ingestion. We also generated a stable cell line Flp-InT-REX-293/Full-CAD (CAD/293) that expressed the H. virescens cadherin. As expected, the cadherin-like protein was mainly localized in the cell membrane. Interestingly, toxin treatment of CAD/293 cells caused this protein to relocalize to cell membrane subdomains. In addition, expression of H. virescens cadherin-like protein affects cell-cell contact and cell membrane integrity when the cells are exposed to activated Cry1Ab/Cry1Ac. 相似文献
994.
ESCRT-I core and ESCRT-II GLUE domain structures reveal role for GLUE in linking to ESCRT-I and membranes 总被引:15,自引:0,他引:15
ESCRT complexes form the main machinery driving protein sorting from endosomes to lysosomes. Currently, the picture regarding assembly of ESCRTs on endosomes is incomplete. The structure of the conserved heterotrimeric ESCRT-I core presented here shows a fan-like arrangement of three helical hairpins, each corresponding to a different subunit. Vps23/Tsg101 is the central hairpin sandwiched between the other subunits, explaining the critical role of its "steadiness box" in the stability of ESCRT-I. We show that yeast ESCRT-I links directly to ESCRT-II, through a tight interaction of Vps28 (ESCRT-I) with the yeast-specific zinc-finger insertion within the GLUE domain of Vps36 (ESCRT-II). The crystal structure of the GLUE domain missing this insertion reveals it is a split PH domain, with a noncanonical lipid binding pocket that binds PtdIns3P. The simultaneous and reinforcing interactions of ESCRT-II GLUE domain with membranes, ESCRT-I, and ubiquitin are critical for ubiquitinated cargo progression from early to late endosomes. 相似文献
995.
The analytical quality of point-of-care testing in the 'QAAMS' model for diabetes management in Australian aboriginal medical services
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Shephard MD Gill JP 《The Clinical biochemist. Reviews / Australian Association of Clinical Biochemists》2006,27(4):185-190
Type 2 diabetes mellitus and its major complication, renal disease, represent one of the most significant contemporary health problems facing Australia's Indigenous Aboriginal People. The Australian Government-funded Quality Assurance for Aboriginal Medical Services Program (QAAMS) provides a framework by which on-site point-of-care testing (POCT) for haemoglobin A1c (HbA(1c)) and now urine albumin:creatinine ratio (ACR) can be performed to facilitate better diabetes management in Aboriginal medical services. This paper provides updated evidence for the analytical quality of POCT in the QAAMS Program. The median imprecision for point-of-care (POC) HbA(1c) and urine ACR quality assurance (QA) testing has continually improved over the past six and half years, stabilising at approximately 3% for both analytes and proving analytically sound in Aboriginal hands. For HbA(1c), there was no statistical difference between the imprecision achieved by QAAMS and laboratory users of the Bayer DCA 2000 since the QAAMS program commenced (QAAMS CV 3.6% +/- 0.52, laboratory CV 3.4% +/- 0.42; p = 0.21, paired t-test). The Western Pacific Island of Tonga recently joined the QAAMS HbA(1c) Program indicating that the QAAMS model can also be applied internationally in other settings where the prevalence of diabetes is high. 相似文献
996.
Daljit Singh Arora Paramjit Kaur Gill 《World journal of microbiology & biotechnology》2005,21(6-7):1021-1028
Summary The present work reports the production of laccase, lignin peroxidase and manganese peroxidase by the little studied white-rot
fungus Phlebia floridensis under a variety of nutritional and physicochemical conditions. Among the different media and supplements the highest yields
of laccase, lignin peroxidase and manganese peroxidase were recorded in the presence of sugarcane bagasse, wheat straw and
rice straw, respectively. Laccase and manganese peroxidase activities were best expressed at a pH of 4.5 while lignin peroxidase
was optimally active at a lower pH. Laccase proved to be much more thermostable as compared to the other two enzymes. 相似文献
997.
Arun Dev Sharma Prabhjot Kaur Gill Sukhdev Singh Bhullar Prabhjeet Singh 《World journal of microbiology & biotechnology》2005,21(6-7):929-932
Summary An extracellular inulinase (fructanase)-producing strain of Penicillium purpurogenum was isolated from the rhizosphere soil of chicory. Conidia of this selected strain were subjected to simultaneous treatment
with NTG–UV (N-methyl-N′-nitro-N-nitrosoguanidine and ultraviolet radiation) and EtBr–UV (Ethidium bromide–ultraviolet radiation). After mutagenesis, colonies
were screened and among them a few were selected to carry out the inulinase study, which showed a significantly higher inulinase
activity with higher I/S (inulin/sucrose) ratio in all the selected colonies, indicating enhancement of inulinase production
after mutagenic treatments in all the selected mutants. 相似文献
998.
Alexander R Balasundaram A Batchelor M Brookings D Crépy K Crabbe T Deltent MF Driessens F Gill A Harris S Hutchinson G Kulisa C Merriman M Mistry P Parton T Turner J Whitcombe I Wright S 《Bioorganic & medicinal chemistry letters》2008,18(15):4316-4320
4-(1,3-Thiazol-2-yl)morpholine derivatives have been identified as potent and selective inhibitors of phosphoinositide 3-kinase. The SAR data of selected examples are presented and the in vivo profiling of compound 18 is shown to demonstrate the utility of this class of compounds in xenograft models of tumor growth. 相似文献
999.
Beveridge TJ Gill KE Hanlon CA Porrino LJ 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2008,363(1507):3257-3266
Cocaine users display profound impairments in executive function. Of all the components of executive function, inhibition, or the ability to withhold responding, has been studied the most extensively and may be most impaired. Consistent with these deficits, evidence from imaging studies points to dysregulation in medial and ventromedial prefrontal cortices, areas activated during performance of inhibition tasks. Other aspects of executive function including updating, shifting and decision making are also deficient in cocaine users, and these deficits are paralleled by abnormalities in patterns of prefrontal cortical activation. The extent to which cocaine plays a role in these effects, however, is not certain, and cannot be determined solely on the basis of human studies. Investigations using a non-human primate model of increasing durations of cocaine exposure revealed that initially the effects of cocaine were restricted to ventromedial and orbital prefrontal cortices, but as exposure was extended the intensity and spatial extent of the effects on functional activity also expanded rostrally and laterally. Given the spatial overlap in prefrontal pathology between human and monkey studies, these longitudinal mapping studies in non-human primates provide a unique window of understanding into the dynamic neural changes that are occurring early in human cocaine abuse. 相似文献
1000.
Dean C. Thorburn David L. Morgan Andrew J. Rowland Howard S. Gill Eric Paling 《Environmental Biology of Fishes》2008,83(2):139-145
The dwarf sawfish, Pristis clavata, was captured in marine waters of King Sound and estuarine waters of the Fitzroy, May and Robinson Rivers, in the Kimberley
region of Western Australia. Observations of sexual maturity and annuli present on vertebrae suggest that the estuarine waters
of at least the Fitzroy River act as a nursery for the species, where immature individuals may remain for at least 3 years.
The capture of immature individuals in excess of 2,330 mm TL during the current study in addition to Peverell’s (Peverell
in Environ Biol Fishes 73:391–402, 2005) record of a mature male measuring 3,060 mm TL implies that the species may attain
far greater lengths than previously reported and that the common name may not be entirely appropriate. In contrast to the
sympatric freshwater sawfish Pristis microdon, the number of rostral teeth of individual P. clavata can not be used to differentiate males from females, with both sexes possessing an average of 42 rostral teeth. 相似文献