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Related Concept Videos

DNA Topoisomerases02:02

DNA Topoisomerases

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Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
Types and Mechanism of action
Topoisomerases are divided into two main types. ...
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Conservative Site-specific Recombination and Phase Variation02:53

Conservative Site-specific Recombination and Phase Variation

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Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
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Translesion DNA Polymerases02:10

Translesion DNA Polymerases

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Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
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Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

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Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
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DNA Helicases00:55

DNA Helicases

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DNA unwinding helicase enzymes are a type of motor protein. Motor proteins can translocate along filaments or polymers using energy generated from ATP hydrolysis. Helicases are involved in all the important cellular processes where DNA unwinding is required, such as DNA replication, repair, recombination, and transcription. They are present in all living organisms, but vary in their structure, function, and mechanism of action. For example, in prokaryotes, DnaB helicase binds and translocates...
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Overview of Myosin Structure and Function01:15

Overview of Myosin Structure and Function

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Myosins are a family of molecular motor proteins, first identified in the skeletal muscles, where they are responsible for muscle contraction. Along with their role in muscle contraction, these proteins also play a role in the intracellular transport of molecules and vesicles. There are twenty-four classes of myosins based on their domain sequence and organization. Of the twenty-four, six classes (Myosin I, Myosin II, Myosin V, Myosin VI, Myosin VII, and Myosin X)  have been well...
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Updated: Jun 1, 2025

Simple and Fast Rolling Circle Amplification-Based Detection of Topoisomerase 1 Activity in Crude Biological Samples
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Multifunctional Mycobacterial Topoisomerases with Distinctive Features.

Iqball Faheem1, Valakunja Nagaraja1,2,3

  • 1Department of Microbiology and Cell Biology, Indian Institute of Science, C.V. Raman Avenue, Bangalore 560012, India.

ACS Infectious Diseases
|January 18, 2025
PubMed
Summary
This summary is machine-generated.

Tuberculosis (TB) treatment faces challenges from drug resistance. This review explores DNA topoisomerases, essential enzymes in Mycobacterium tuberculosis, as promising targets for novel antibacterial drugs to combat resistant TB strains.

Keywords:
DNA TopologyDNA gyraseMycobacterium tuberculosisTopoisomerase ITopoisomerase Inhibitors

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Area of Science:

  • Microbiology
  • Biochemistry
  • Drug Discovery

Background:

  • Tuberculosis (TB) remains a significant global health threat, exacerbated by multidrug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) strains.
  • Mycobacterium tuberculosis exhibits remarkable adaptability, complicating treatment and necessitating novel therapeutic strategies.
  • DNA topoisomerases are crucial enzymes for managing DNA topology during cellular processes and represent validated targets for antibacterial drug development.

Purpose of the Study:

  • To review the organization, structure, function, and regulation of DNA gyrase and Topoisomerase I (TopoI) in Mycobacterium tuberculosis.
  • To explore the potential of these enzymes as targets for developing new anti-TB therapeutics.
  • To provide insights into existing and emerging inhibitors of mycobacterial topoisomerases.

Main Methods:

  • Comparative analysis of mycobacterial DNA gyrase and TopoI structures and biochemical properties against counterparts from other bacteria.
  • Review of established DNA gyrase inhibitors and novel bacterial topoisomerase inhibitors (NBTIs).
  • Update on TopoI-specific compounds, with a focus on those targeting mycobacteria.

Main Results:

  • DNA topoisomerases in M. tuberculosis possess unique characteristics compared to other bacterial species.
  • These enzymes are essential for pathogen survival, highlighting their potential as drug targets.
  • A range of inhibitors targeting DNA gyrase and TopoI exist, with ongoing development of novel agents.

Conclusions:

  • Targeting DNA topoisomerases in Mycobacterium tuberculosis offers a promising avenue for developing new drugs against drug-resistant TB.
  • Understanding the specific properties of mycobacterial topoisomerases is key to designing effective and selective inhibitors.
  • Further research into novel bacterial topoisomerase inhibitors (NBTIs) and TopoI-specific compounds is warranted for combating TB.