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71.
Steffen N. Lindner Sandra Knebel Srinivas R. Pallerla Siegfried M. Schoberth Volker F. Wendisch 《Applied microbiology and biotechnology》2010,87(2):703-713
The Corynebacterium glutamicum gene cg2091 is encoding a polyphosphate (PolyP)/ATP-dependent glucokinase (PPGK). Previous work demonstrated the association
of PPGK to PolyP granules. The deduced amino acid sequence of PPGK shows 45% sequence identity to PolyP/ATP glucomannokinase
of Arthrobacter sp. strain KM and 50% sequence identity to PolyP glucokinase of Mycobacterium tuberculosis H37Rv. PPGK from C. glutamicum was purified from recombinant Escherichia coli. PolyP was highly preferred over ATP and other NTPs as substrate and with respect to the tested PolyPs differing in chain
length; the protein was most active with PolyP75. Gel filtration analysis revealed that PolyP supported the formation of homodimers of PPGK and that PPGK was active as a
homodimer. A ppgK deletion mutant (ΔppgK) showed slowed growth in minimal medium with maltose as sole carbon source. Moreover, in minimal medium containing 2 to 4%
(w/v) glucose as carbon source, ΔppgK grew to lower final biomass concentrations than the wild type. Under phosphate starvation conditions, growth of ΔppgK was reduced, and growth of a ppgK overexpressing strain was increased as compared to wild type and empty vector control, respectively. Thus, under conditions
of glucose excess, the presence of PPGK entailed a growth advantage. 相似文献
72.
Parasuram R Lee JS Yin P Somarowthu S Ondrechen MJ 《Journal of bioinformatics and computational biology》2010,8(Z1):1-15
A new approach to the functional classification of protein 3D structures is described with application to some examples from structural genomics. This approach is based on functional site prediction with THEMATICS and POOL. THEMATICS employs calculated electrostatic potentials of the query structure. POOL is a machine learning method that utilizes THEMATICS features and has been shown to predict accurate, precise, highly localized interaction sites. Extension to the functional classification of structural genomics proteins is now described. Predicted functionally important residues are structurally aligned with those of proteins with previously characterized biochemical functions. A 3D structure match at the predicted local functional site then serves as a more reliable predictor of biochemical function than an overall structure match. Annotation is confirmed for a structural genomics protein with the ribulose phosphate binding barrel (RPBB) fold. A putative glucoamylase from Bacteroides fragilis (PDB ID 3eu8) is shown to be in fact probably not a glucoamylase. Finally a structural genomics protein from Streptomyces coelicolor annotated as an enoyl-CoA hydratase (PDB ID 3g64) is shown to be misannotated. Its predicted active site does not match the well-characterized enoyl-CoA hydratases of similar structure but rather bears closer resemblance to those of a dehalogenase with similar fold. 相似文献
73.
Prakash Peddi Charles W. Loftin Jennifer S. Dickey Jessica M. Hair Kara J. Burns Khaled Aziz Dave C. Francisco Mihalis I. Panayiotidis Olga A. Sedelnikova William M. Bonner Thomas A. Winters Alexandros G. Georgakilas 《Free radical biology & medicine》2010,48(10):1435-1443
DNA-dependent protein kinase (DNA-PK) is a key non-homologous-end-joining (NHEJ) nuclear serine/threonine protein kinase involved in various DNA metabolic and damage signaling pathways contributing to the maintenance of genomic stability and prevention of cancer. To examine the role of DNA-PK in processing of non-DSB clustered DNA damage, we have used three models of DNA-PK deficiency, i.e., chemical inactivation of its kinase activity by the novel inhibitors IC86621 and NU7026, knockdown and complete absence of the protein in human breast cancer (MCF-7) and glioblastoma cell lines (MO59-J/K). A compromised DNA-PK repair pathway led to the accumulation of clustered DNA lesions induced by γ-rays. Tumor cells lacking protein expression or with inhibited kinase activity showed a marked decrease in their ability to process oxidatively induced non-DSB clustered DNA lesions measured using a modified version of pulsed-field gel electrophoresis or single-cell gel electrophoresis (comet assay). In all cases, DNA-PK inactivation led to a higher level of lesion persistence even after 24–72 h of repair. We suggest a model in which DNA-PK deficiency affects the processing of these clusters first by compromising base excision repair and second by the presence of catalytically inactive DNA-PK inhibiting the efficient processing of these lesions owing to the failure of DNA-PK to disassociate from the DNA ends. The information rendered will be important for understanding not only cancer etiology in the presence of an NHEJ deficiency but also cancer treatments based on the induction of oxidative stress and inhibition of cluster repair. 相似文献
74.
Balachandar Venkatesan Sumanth D. Prabhu Kaliyamurthi Venkatachalam Srinivas Mummidi Anthony J. Valente Robert A. Clark Patrice Delafontaine Bysani Chandrasekar 《Cellular signalling》2010,22(5):809-820
The anthracycline antibiotic doxorubicin (DOX) is a potent cancer chemotherapeutic agent that exerts both acute and chronic cardiotoxicity. Here we show that in adult mouse cardiomyocytes, DOX activates (i) the pro-apoptotic p53, (ii) p38MAPK and JNK, (iii) Bax translocation, (iv) cytochrome c release, and (v) caspase 3. Further, it (vi) inhibits expression of anti-apoptotic Akt, Bcl-2 and Bcl-xL, and (vii) induces internucleosomal degradation and cell death. WNT1-inducible signaling pathway protein-1 (WISP1), a CCN family member and a matricellular protein, inhibits DOX-mediated cardiomyocyte death. WISP1 inhibits DOX-induced p53 activation, p38 MAPK and JNK phosphorylation, Bax translocation to mitochondria, and cytochrome c release into cytoplasm. Additionally, WISP1 reverses DOX-induced suppression of Bcl-2 and Bcl-xL expression and Akt inhibition. The pro-survival effects of WISP1 were recapitulated by the forced expression of mutant p53, wild-type Bcl-2, wild-type Bcl-xL, or constitutively active Akt prior to DOX treatment. WISP1 also induces the pro-survival factor Survivin via PI3K/Akt signaling. Overexpression of wild-type, but not mutant Survivin, blunts DOX cytotoxicity. Further, WISP1 stimulates PI3K–Akt-dependent GSK3β phosphorylation and β-catenin nuclear translocation. Importantly, WISP1 induces its own expression. Together, these results provide important insights into the cytoprotective effects of WISP1 in cardiomyocytes, and suggest a potential therapeutic role for WISP1 in DOX-induced cardiotoxicity. 相似文献
75.
76.
Monocrotophos inhibited monoamine oxidase (MAO) activity both in vitro and in vivo in liver, kidney and brain areas of albino rats. In vitro effect was more pronounced than the in vivo effect. During in vivo daily treatment with sublethal doses of Monocrotophos, the MAO activity was significantly inhibited after 1h to 7 days of treatments. Later recovery of inhibition was noticed which might be attributed to the enhanced absorption of Monocrotophos to protein and fat bodies or enhanced metabolic dispositional mechanisms. Brain areas exhibit varied responses to Monocrotophos toxicity. 相似文献
77.
Vince JE Wong WW Khan N Feltham R Chau D Ahmed AU Benetatos CA Chunduru SK Condon SM McKinlay M Brink R Leverkus M Tergaonkar V Schneider P Callus BA Koentgen F Vaux DL Silke J 《Cell》2007,131(4):682-693
XIAP prevents apoptosis by binding to and inhibiting caspases, and this inhibition can be relieved by IAP antagonists, such as Smac/DIABLO. IAP antagonist compounds (IACs) have therefore been designed to inhibit XIAP to kill tumor cells. Because XIAP inhibits postmitochondrial caspases, caspase 8 inhibitors should not block killing by IACs. Instead, we show that apoptosis caused by an IAC is blocked by the caspase 8 inhibitor crmA and that IAP antagonists activate NF-kappaB signaling via inhibtion of cIAP1. In sensitive tumor lines, IAP antagonist induced NF-kappaB-stimulated production of TNFalpha that killed cells in an autocrine fashion. Inhibition of NF-kappaB reduced TNFalpha production, and blocking NF-kappaB activation or TNFalpha allowed tumor cells to survive IAC-induced apoptosis. Cells treated with an IAC, or those in which cIAP1 was deleted, became sensitive to apoptosis induced by exogenous TNFalpha, suggesting novel uses of these compounds in treating cancer. 相似文献
78.
Harsh Chauhan Srinivas A. Desai Paramjit Khurana 《Plant Cell, Tissue and Organ Culture》2007,91(3):191-199
An efficient genotype independent, in vitro regeneration system was developed for nine popular Indian wheat cultivars, three
each of Triticum aestivum L. viz., CPAN1676, HD2329 and PBW343, Triticum durum Desf. viz., PDW215, PDW233 and WH896, and Triticum dicoccum Schrank. Schubl. viz., DDK1001, DDK1025 and DDK1029, by manipulating the concentration and time of exposure to the growth
regulator, thidiazuron (TDZ). A total of 18 (for immature inflorescence and embryo explant) and six (for mature embryo explant)
different combinations of growth regulators were tried for callusing and regeneration, respectively. Media combination with
low concentration of TDZ (2.2 μM) in combination to auxin and/or cytokinin (depending upon culture stage), was found to be
effective for immature and mature explants. Compact, nodular and highly embryogenic calli were obtained by using immature
embryo, immature inflorescence and mature embryo explants, and regeneration frequency up to 25 shoots/explant with an overall
80% regeneration was achieved. Comparable regeneration frequency was achieved for mature embryo explants. No separate hormone
combination for rooting was required and plantlets ready to transfer to soil could be obtained in a short period of 8–10 weeks.
This protocol can be used for raising transgenic plants for functional genomics analysis of agronomically important traits
in the three species of wheat. 相似文献
79.
Mitogen-activated protein kinase kinase-4 promotes cell survival by decreasing PTEN expression through an NF kappa B-dependent pathway 总被引:2,自引:0,他引:2
Xia D Srinivas H Ahn YH Sethi G Sheng X Yung WK Xia Q Chiao PJ Kim H Brown PH Wistuba II Aggarwal BB Kurie JM 《The Journal of biological chemistry》2007,282(6):3507-3519
80.
Balaji KN Goyal G Narayana Y Srinivas M Chaturvedi R Mohammad S 《Microbes and infection / Institut Pasteur》2007,9(3):271-281
Ectopic expression of the Mycobacterium tuberculosis PE-family gene Rv1818c, triggers apoptosis in the mammalian Jurkat T cells, which is blocked by anti-apoptotic protein Bcl-2. Although complete overlap is not observed, a considerable proportion of cellular pools of ectopically expressed Rv1818c localizes to mitochondria. However, recombinant Rv1818c does not trigger release of cytochrome c from isolated mitochondria even though Rv1818c protein induced apoptosis of Jurkat T cells. Apoptosis induced by Rv1818c is blocked by the broad-spectrum caspase inhibitory peptide zVAD-FMK. Unexpectedly, Rv1818c-induced apoptosis is not blocked in a Jurkat sub-clone deficient for caspase-8 (JI 9.2) or in cells where caspase-9 function is inhibited or expression of caspase-9 reduced by siRNA, arguing against a central role for these caspases in Rv1818c-induced apoptotic signaling. Depleting cellular pools of the mitochondrial protein Smac/DIABLO substantially reduces apoptosis consistent with mitochondrial involvement in this death pathway. We present evidence that Rv1818c-induced apoptosis is blocked by the co-transfection of an endogenous inhibitor of caspase activation, XIAP in T cells. Additionally, Rv1818c is released into extracellular environment via exosomes secreted by M. tuberculosis infected BM-DC's and macrophages. Furthermore, the extracellular Rv1818c protein can be detected in T cells co-cultured with infected BM-DC's. Taken together, these data suggest that Rv1818c-induced apoptotic signaling is likely regulated in part by the Smac-dependent activation of caspases in T cells. 相似文献