Evidence for the Role of DNA Strand Passage in the Mechanism of Action of Microcin B17 on DNA Gyrase†

DNA topos (topoisomerases) are complex, multisubunit enzymes that remodel DNA topology. Members of the type II topo family function by passing one segment of duplex DNA through a transient break in another, a process that consumes two molecules of ATP and requires the co-ordinated action of multiple domains. Recent structural data on type II topo ATPase regions, which activate and enforce the directionality of DNA strand passage, have highlighted how ATP physically controls the catalytic cycle of the enzyme. Structural and biochemical studies of specialized DNA-binding domains in two paralogous bacterial type IIA topos (DNA gyrase and topo IV) show how these enzymes selectively negatively supercoil or decatenate DNA. Taken together, these findings expand our understanding of how disparate functional elements work together to co-ordinate the type II topo mechanism.

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Coupling ATP hydrolysis to DNA strand passage in type IIA DNA topoisomerases

Biochemical Society Transactions ◽

10.1042/bst0331460 ◽

2005 ◽

Vol 33 (6) ◽

pp. 1460-1464 ◽

Cited By ~ 13

Author(s):

A. Maxwell ◽

L. Costenaro ◽

S. Mitelheiser ◽

A.D. Bates

Keyword(s):

Atp Hydrolysis ◽

Dna Gyrase ◽

Energy Coupling ◽

Dna Topoisomerases ◽

Structural Work ◽

Structural Details ◽

Negative Supercoiling ◽

Topo Ii ◽

Dna Strand ◽

Strand Passage

Type IIA topos (topoisomerases) catalyse topological conversions of DNA through the passage of one double strand through a transient break in another. In the case of the archetypal enzyme, DNA gyrase, it has always been apparent that the enzyme couples the free energy of ATP hydrolysis to the introduction of negative supercoiling, and the structural details of this process are now becoming clearer. The homologous type IIA enzymes such as topo IV and eukaryotic topo II also require ATP and it has more recently been shown that the energy of hydrolysis is coupled to a reduction of supercoiling or catenation (linking) beyond equilibrium. The mechanism behind this effect is less clear. We review the energy coupling process in both classes of enzyme and describe recent mechanistic and structural work on gyrase that addresses the mechanism of energy coupling.

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SOME ASPECTS OF THE FUNCTION OF FSH- AND LH-LIKE HORMONES IN NORMAL AND HYPOPHYSECTOMIZED FEMALE RATS, IN CONNECTION WITH RESERPINE ADMINISTRATION

Acta Endocrinologica ◽

10.1530/acta.0.0490028 ◽

1965 ◽

Vol 49 (1) ◽

pp. 28-38

Author(s):

M. Grönroos ◽

E. Mäkinen ◽

K. Lahtinen ◽

R. Tirri

Keyword(s):

Mechanism Of Action ◽

Biological Effect ◽

Female Rats ◽

Histological Picture ◽

Peripheral Effect ◽

Pituitary Secretion

ABSTRACT The effect of reserpine on the secretion of FSH and LH was studied as well as the role of the peripheral effect of reserpine after hypophysectomy. The results in the unoperated animals suggest that reserpine inhibits the pituitary secretion of both FSH and LH. Both these hormones combined with reserpine had a very different biological effect than was seen without reserpine. HCG (LH-like) and particularly PMS (FSH-like) hormones combined with reserpine caused definite enlargement of the ovaries. In the hypophysectomized groups, the effect of the PMS and HCG hormones administered together with reserpine or without it was the same with regard to the weight of the ovaries, but not with regard to their histological picture. On the basis of these results, reserpine may be said to have a peripheral effect although the nature of its mechanism of action is difficult to state. Reserpine probably affects the ovaries by inhibiting the follicular cycle and, consequently, the formation of new and more mature follicles.

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Role of Flavonoids in Neurodegenerative Disorders with Special Emphasis on Tangeritin

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527318666190916141934 ◽

2019 ◽

Vol 18 (8) ◽

pp. 581-597 ◽

Cited By ~ 1

Author(s):

Ambreen Fatima ◽

Yasir Hasan Siddique

Keyword(s):

Medicinal Plants ◽

Mechanism Of Action ◽

Neurodegenerative Disorders ◽

Treatment Strategies ◽

Dietary Supplementation ◽

Plant Polyphenols ◽

Promising Candidate ◽

Naturally Occurring ◽

The Brain

Flavonoids are naturally occurring plant polyphenols found universally in all fruits, vegetables and medicinal plants. They have emerged as a promising candidate in the formulation of treatment strategies for various neurodegenerative disorders. The use of flavonoid rich plant extracts and food in dietary supplementation have shown favourable outcomes. The present review describes the types, properties and metabolism of flavonoids. Neuroprotective role of various flavonoids and the possible mechanism of action in the brain against the neurodegeneration have been described in detail with special emphasis on the tangeritin.

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The mechanism of action of N-acetylcysteine (NAC): The emerging role of H2S and sulfane sulfur species

Pharmacology & Therapeutics ◽

10.1016/j.pharmthera.2021.107916 ◽

2021 ◽

pp. 107916

Author(s):

Brandán Pedre ◽

Uladzimir Barayeu ◽

Daria Ezeriņa ◽

Tobias P. Dick

Keyword(s):

Mechanism Of Action ◽

Sulfur Species ◽

Sulfane Sulfur

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The role of ascorbic acid combined exposure on Imidacloprid-induced oxidative stress and genotoxicity in Nile tilapia

Scientific Reports ◽

10.1038/s41598-021-94020-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Islam M. El-Garawani ◽

Elsayed A. Khallaf ◽

Alaa A. Alne-na-ei ◽

Rehab G. Elgendy ◽

Gaber A. M. Mersal ◽

...

Keyword(s):

Oxidative Stress ◽

Ascorbic Acid ◽

Nile Tilapia ◽

Protective Agent ◽

Strand Breaks ◽

Gill Cells ◽

Significant Amelioration ◽

Neonicotinoid Insecticide ◽

Dna Strand

AbstractImidacloprid (Imid), a systemic neonicotinoid insecticide, is broadly used worldwide. It is reported to contaminate aquatic systems. This study was proposed to evaluate oxidative stress and genotoxicity of Imid on Nile tilapia (Oreochromis niloticus) and the protective effect of ascorbic acid (Asc). O. niloticus juveniles (30.4 ± 9.3 g, 11.9 ± 1.3 cm) were divided into six groups (n = 10/replicate). For 21 days, two groups were exposed to sub-lethal concentrations of Imid (8.75 ppm, 1/20 of 72 h-LC50 and 17.5 ppm, 1/10 of 72 h-LC50); other two groups were exposed to Asc (50 ppm) in combination with Imid (8.75 and 17.5 ppm); one group was exposed to Asc (50 ppm) in addition to a group of unexposed fish which served as controls. Oxidative stress was assessed in the liver where the level of enzymatic activities including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in addition to mRNA transcripts and, Lipid peroxidation (LPO) were evaluated. Moreover, mitotic index (MI) and comet assay were performed, in addition, the erythrocytic micronucleus (MN), and nuclear abnormalities (NA) were observed to assess genotoxicity in fish. Imid exposure induced significant (p ˂ 0.05) changes in the antioxidant profile of the juveniles' liver by increasing the activities and gene expression of SOD, CAT and GPX as well as elevating the levels of LPO. DNA strand breaks in gill cells, erythrocytes and hepatocytes along with erythrocytic MN and NA were also significantly elevated in Imid-exposed groups. MI showed a significant (p ˂ 0.05) decrease associated with Imid exposure. Asc administration induced a significant amelioration towards the Imid toxicity (8.75 and 17.5 ppm). A significant protective potency against the genotoxic effects of Imid was evidenced in Asc co-treated groups. Collectively, results highlight the importance of Asc as a protective agent against Imid-induced oxidative stress and genotoxicity in O. niloticus juveniles.

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