6 results match your criteria gyrase-targeted drugs

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The pentapeptide-repeat protein, MfpA, interacts with mycobacterial DNA gyrase as a DNA T-segment mimic.

Proc Natl Acad Sci U S A 2021 Mar;118(11)

Department of Biological Chemistry, John Innes Centre, NR4 7UH Norwich, United Kingdom;

DNA gyrase, a type II topoisomerase, introduces negative supercoils into DNA using ATP hydrolysis. The highly effective gyrase-targeted drugs, fluoroquinolones (FQs), interrupt gyrase by stabilizing a DNA-cleavage complex, a transient intermediate in the supercoiling cycle, leading to double-stranded DNA breaks. MfpA, a pentapeptide-repeat protein in mycobacteria, protects gyrase from FQs, but its molecular mechanism remains unknown. Read More

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Identification of new DNA gyrase inhibitors based on bioactive compounds from streptomyces: structure-based virtual screening and molecular dynamics simulations approaches.

J Biomol Struct Dyn 2020 02 27;38(3):791-806. Epub 2019 Mar 27.

Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

DNA gyrase enzyme has vital role in bacterial survival and can be considered as a potential drug target. Owing to the appearance of resistance to gyrase-targeted drugs, especially fluoroquinolone, screening new compounds which bind more efficiently to the mutant binding pocket is essential. Hence, in this work, using Smina Autodock and through structure-based virtual screening of StreptomeDB, several natural products were discovered based on the SimocyclinoneD8 (SD8) binding pocket of GyrA subunit of DNA gyrase. Read More

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February 2020

New Strategy on Antimicrobial-resistance: Inhibitors of DNA Replication Enzymes.

Authors:
Lanhua Yi Xin Lü

Curr Med Chem 2019 ;26(10):1761-1787

College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi Province 712100, China.

Background: Antimicrobial resistance is found in all microorganisms and has become one of the biggest threats to global health. New antimicrobials with different action mechanisms are effective weapons to fight against antibiotic-resistance.

Objective: This review aims to find potential drugs which can be further developed into clinic practice and provide clues for developing more effective antimicrobials. Read More

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Identification of novel bacterial DNA gyrase inhibitors: An in silico study.

Res Pharm Sci 2016 May-Jun;11(3):250-8

Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, I.R. Iran.

Owing to essential role in bacterial survival, DNA gyrase has been exploited as a validated drug target. However, rapidly emerging resistance to gyrase-targeted drugs such as widely utilized fluoroquinolones reveals the necessity to develop novel compounds with new mechanism of actions against this enzyme. Here, an attempt has been made to identify new drug-like molecules for Shigella flexneri DNA gyrase inhibition through in silico approaches. Read More

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Exploiting bacterial DNA gyrase as a drug target: current state and perspectives.

Appl Microbiol Biotechnol 2011 Nov 9;92(3):479-97. Epub 2011 Sep 9.

Department Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK.

DNA gyrase is a type II topoisomerase that can introduce negative supercoils into DNA at the expense of ATP hydrolysis. It is essential in all bacteria but absent from higher eukaryotes, making it an attractive target for antibacterials. The fluoroquinolones are examples of very successful gyrase-targeted drugs, but the rise in bacterial resistance to these agents means that we not only need to seek new compounds, but also new modes of inhibition of this enzyme. Read More

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November 2011

Quinolones share a common interaction domain on topoisomerase II with other DNA cleavage-enhancing antineoplastic drugs.

Biochemistry 1997 Mar;36(10):2919-24

Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA.

Topoisomerase II is the cytotoxic target for a number of clinically relevant antineoplastic drugs. Despite the fact that these agents differ significantly in structure, a previous study [Corbett, A. H. Read More

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