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1.
Manickam Sugumaran Karin Schinkmann Hemalata Dali 《Archives of insect biochemistry and physiology》1990,14(2):93-109
The mechanism of oxidation of 1,2-dehydro-N-acetyldopamine (dehydro NADA) was examined to resolve the controversy between our group and Andersen's group regarding the reactive species involved in β-sclerotization. While Andersen has indicated that dehydro NADA quinone is the β-sclerotizing agent [Andersen, 1989], we have proposed quinone methides as the reactive species for this process [Sugumaran, 1987; Sugumaran, 1988]. Since dehydro NADA quinone has not been isolated or identified till to date, we studied the enzymatic oxidation of dehydro NADA in the presence of quinone traps to characterize this intermediate. Accordingly, both N-acetylcysteine and o-phenylenediamine readily trapped the transiently formed dehydro NADA quinone as quinone adducts. Interestingly, when the enzymatic oxidation was performed in the presence of o-aminophenol or different catechols, adduct formation between the dehydro NADA side chain and the additives had occurred. The structure of the adducts is in conformity with the generation and reactions of dehydro NADA quinone methide (or its radical). This, coupled with the fact that 4-hydroxyl or amino-substituted quinones instantly transformed into p-quinonoid structure, indicates that dehydro NADA quinone is only a transient intermediate and that it is the dehydro NADA quinone methide that is the thermodynamically stable product. However, since this compound is chemically more reactive due to the presence of both quinone methide and acylimine structure on it, the two side chain carbon atoms are “activated.” Based on these considerations, it is suggested that the quinone methide derived from dehydro NADA is the reactive species responsible for cross-link formation between dehydro NADA and cuticular components during β-sclerotization. 相似文献
2.
Manickam Sugumaran Steven J. Saul Victor Semensi 《Archives of insect biochemistry and physiology》1988,9(4):269-281
The mechanism of formation of quinone methide from the sclerotizing precursor N-acetyldopamine (NADA) was studied using three different cuticular enzyme systems viz. Sarcophaga bullata larval cuticle, Manduca sexta pharate pupae, and Periplaneta americana presclerotized adult cuticle. All three cuticular samples readily oxidized NADA. During the enzyme-catalyzed oxidation, the majority of NADA oxidized became bound covalently to the cuticle through the side chain with the retention of o-diphenolic function, while a minor amount was recovered as N-acetylnorepinephrine (NANE). Cuticle treated with NADA readily released 2-hydroxy-3′,4′-dihydroxyacetophenone on mild acid hydrolysis confirming the operation of quinone methide sclerotization. Attempts to demonstrate the direct formation of NADA-quinone methide by trapping experiments with N-acetylcysteine surprisingly yielded NADA-quinone-N-acetylcysteine adduct rather than the expected NADA-quinone methide-N-acetylcysteine adduct. These results are indicative of NADA oxidation to NADA-quinone and its subsequent isomerization to NADA-quinone methide. Accordingly, all three cuticular samples exhibited the presence of an isomerase, which catalyzed the conversion of NADA-quinone to NADA-quinone methide as evidenced by the formation of NANE—the water adduct of quinone methide. Thus, in association with phenoloxidase, newly discovered quinone methide isomerase seems to generate quinone methides and provide them for quinone methide sclerotization. 相似文献
3.
Thirunavukkarasu Muralisankar Periyakali Saravana Bhavan Subramanian Radhakrishnan Chandirasekar Seenivasan Narasimman Manickam Veeran Srinivasan 《Biological trace element research》2014,160(1):56-66
The present study was conducted to assess the influence of dietary zinc nanoparticles (size 50 nm) on the growth, biochemical constituents, enzymatic antioxidant levels and the nonspecific immune response of the freshwater prawn, Macrobrachium rosenbergii post larvae (PL). The concentrations of dietary supplement zinc nanoparticles (ZnNPs) were 0, 10, 20, 40, 60 and 80 mg kg?1 with the basal diet, and the level of Zn in ZnNP-supplemented diets were 0.71, 10.61, 20.73, 40.73, 60.61 and 80.60 mg kg?1, respectively. ZnNP-incorporated diets were fed to M. rosenbergii PL (initial body weight, 0.18?±?0.02 g) in a triplicate experimental setup for a period of 90 days. ZnNP supplemented feed fed PL up to 60 mg kg?1 showed significantly (P?<?0.05) improved performance in survival, growth and activities of digestive enzymes (protease, amylase and lipase). The concentrations of biochemical constituents (total protein, total amino acid, total carbohydrate and total lipid), total haemocyte count and differential haemocyte count were elevated in 10–60 mg kg?1 ZnNP supplemented feed fed PL. However, the PL fed with 80 mg ZnNPs kg?1 showed negative results. Activities of enzymatic antioxidants [superoxide dismutase (SOD) and catalase (CAT)], metabolic enzymes [glutamate–oxaloacetate transaminase (GOT) and glutamate–pyruvate transaminase (GPT)] and the process of lipid peroxidation (LPO) in the hepatopancreas and muscle showed no significant alterations in 10–60 mg kg?1 ZnNP supplemented feed fed PL. Whereas, 80 mg ZnNPs kg?1 supplemented feed fed PL showed significant elevations in SOD, CAT, LPO, GOT and GPT. Therefore, 80 mg ZnNPs kg?1 was found to be toxic to M. rosenbergii PL. Thus, the study suggests that up to 60 mg ZnNPs kg?1 can be supplemented for regulating survival, growth and immunity of M. rosenbergii. 相似文献
4.
Ishvaria S. Dharshini Rajathirajan Siva Manickam Ranjani Pooja K. R. Ramya Mohandass 《Antonie van Leeuwenhoek》2021,114(12):1977-1989
Antonie van Leeuwenhoek - Biofilm forming bacterium Bacillus novalis PD1 was isolated from the rhizospheric soil of a paddy field. B. novalis PD1 is a Gram-positive, facultatively anaerobic,... 相似文献
5.
6.
Sameena Khan Ankur Garg Arvind Sharma Noelia Camacho Daria Picchioni Adéla?de Saint-Léger Lluís Ribas de Pouplana Manickam Yogavel Amit Sharma 《PloS one》2013,8(6)
Specific activation of amino acids by aminoacyl-tRNA synthetases (aaRSs) is essential for maintaining fidelity during protein translation. Here, we present crystal structure of malaria parasite Plasmodium falciparum tryptophanyl-tRNA synthetase (Pf-WRS) catalytic domain (AAD) at 2.6 Å resolution in complex with L-tryptophan. Confocal microscopy-based localization data suggest cytoplasmic residency of this protein. Pf-WRS has an unusual N-terminal extension of AlaX-like domain (AXD) along with linker regions which together seem vital for enzymatic activity and tRNA binding. Pf-WRS is not proteolytically processed in the parasites and therefore AXD likely provides tRNA binding capability rather than editing activity. The N-terminal domain containing AXD and linker region is monomeric and would result in an unusual overall architecture for Pf-WRS where the dimeric catalytic domains have monomeric AXDs on either side. Our PDB-wide comparative analyses of 47 WRS crystal structures also provide new mechanistic insights into this enzyme family in context conserved KMSKS loop conformations. 相似文献
7.
Saravanakumar Sundararajan Isaivani Jayachandran Muthuswamy Balasubramanyam Viswanathan Mohan Balachandar Venkatesan Nagaraj Manickam 《Journal of cellular biochemistry》2019,120(5):8201-8213
The vicious cycle between hyperinsulinemia and insulin resistance results in the progression of atherosclerosis in the vessel wall. The complex interaction between hyperglycemia and lipoprotein abnormalities promotes the development of atherogenesis. In the early phase of atherosclerosis, macrophage-derived foam cells play an important role in vascular remodeling. Mechanistic target of rapamycin (mTOR) signaling pathway has been identified to play an essential role in the initiation, progression, and complication of atherosclerosis. Recently sestrin2, an antioxidant, was shown to modulate TOR activity and thereby regulating glucose and lipid metabolism. But the role of sestrin2 in monocyte activation is still not clearly understood. Hence, this study is focussed on investigating the role of sestrin2 in monocyte activation under hyperglycemic and dyslipidemic conditions. High-glucose and oxidized low-density lipoprotein (LDL) treatments mediated proinflammatory cytokine production (M1) with a concomitant decrease in the anti-inflammatory cytokine (M2) levels in human monocytic THP1 cells. Both glucose and oxidized LDL (OxLDL) in a dose and time-dependent manner increased the mTOR activation with a marked reduction in the levels of pAMPK and sestrin2 expression. Both high-glucose and OxLDL treatment increased foam cell formation and adhesion of THP1 cells to endothelial cells. Experiments employing activator or inhibitor of adenosine monophosphate kinase (AMPK) as well as overexpression or silencing of sestrin2 indicated that high-glucose mediated monocyte polarization and adhesion of monocytes to the endothelial cells were appeared to be programmed via sestrin2-AMPK-mTOR nexus. Our results evidently suggest that sestrin2 plays a major role in regulating monocyte activation via the AMPK–mTOR-pathway under diabetic and dyslipidemic conditions and also AMPK regulates sestrin2 in a feedback mechanism. 相似文献
8.
Yogavel Manickam Nipun Malhotra Siddhartha Mishra Palak Babbar Abhishek Dusane Benoît Laleu Valeria Bellini Mohamed-Ali Hakimi Alexandre Bougdour Amit Sharma 《PLoS pathogens》2022,18(3)
Toxoplasmosis is caused by Toxoplasma gondii and in immunocompromised patients it may lead to seizures, encephalitis or death. The conserved enzyme prolyl-tRNA synthetase (PRS) is a validated druggable target in Toxoplasma gondii but the traditional ‘single target–single drug’ approach has its caveats. Here, we describe two potent inhibitors namely halofuginone (HFG) and a novel ATP mimetic (L95) that bind to Toxoplasma gondii PRS simultaneously at different neighbouring sites to cover all three of the enzyme substrate subsites. HFG and L95 act as one triple-site inhibitor in tandem and form an unusual ternary complex wherein HFG occupies the 3’-end of tRNA and the L-proline (L-pro) binding sites while L95 occupies the ATP pocket. These inhibitors exhibit nanomolar IC50 and EC50 values independently, and when given together reveal an additive mode of action in parasite inhibition assays. This work validates a novel approach and lays a structural framework for further drug development based on simultaneous targeting of multiple pockets to inhibit druggable proteins. 相似文献
9.
Walkty A Lagacé-Wiens PR Karlowsky JA Hoban DJ Manickam K Adam H Pieroni P Alfa M 《Canadian journal of microbiology》2012,58(3):345-349
Urinary tract infections are common. Few published studies have demonstrated the change in Escherichia coli urinary isolate antimicrobial susceptibility over time within a given area and (or) population. The purpose of this study was to evaluate the change in susceptibility of E. coli clinical isolates obtained from urine specimens at a single institution over a period of 10 years. The microbiology laboratory information system at St. Boniface Hospital (Winnipeg, Manitoba, Canada) was searched retrospectively from 1 January 2000 to 31 December 2009, for all E. coli isolates from either a midstream or catheter urine source that had susceptibility testing performed. Only one isolate per patient was included during the entire study period. Antimicrobial susceptibility testing was carried out with either a Microscan instrument (pre-April 2004) or a Vitek instrument (May 2004 onwards). In total, 7353 E. coli urinary isolates were included for evaluation. Ciprofloxacin susceptibility declined significantly, from 99% in 2000 to 85% in 2009 (p < 0.0001). A small but statistically significant decline in susceptibility was also observed for ampicillin, cefazolin, trimethoprim-sulfamethoxazole, gentamicin, and nitrofurantoin. These data suggest that certain antimicrobials recommended for the treatment of urinary tract infections (ciprofloxacin, trimethoprim-sulfamethoxazole) may no longer be optimal. 相似文献
10.
Ayyanar Manickam Els J. M. Van Damme Kandasamy Kalaiselvi Peter Verhaert Willy J. Peumans 《Physiologia plantarum》1996,97(3):524-530
Until now no 'early-methionine-labelled' (Em) proteins have been reported in the Fabaceae. To check whether a previously isolated low-molecular mass albumin from dry mung bean embryonic axes possibly corresponded to an Em-like protein, the protein was purified, sequenced and its cDNA clone isolated and characterized. N-terminal sequencing of cyanogen bromide cleavage products of the protein revealed homology with previously described Em-like proteins from other species. Analysis of cDNA clones encoding the mung bean Em protein revealed the presence of two classes of Em proteins and confirmed their homology to the previously characterized Em-like proteins. In vivo labelling and northern blot analysis further demonstrated that the mung bean protein is synthesized during early germination of the axes and that abscisic acid (ABA) extends its synthesis. It appears, therefore, that legumes also contain maturation-specific, ABA-responsive Em-like proteins. 相似文献