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Related Concept Videos

ATP Synthase: Mechanism01:48

ATP Synthase: Mechanism

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In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
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ATP Synthase: Structure01:18

ATP Synthase: Structure

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ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP...
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The Electron Transport Chain01:30

The Electron Transport Chain

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The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
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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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Targets for Drug Action: Overview01:26

Targets for Drug Action: Overview

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Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
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Cholinergic Antagonists: Chemistry and Structure-Activity Relationship01:29

Cholinergic Antagonists: Chemistry and Structure-Activity Relationship

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Cholinergic antagonists bind to cholinergic receptors and limit the effects of acetylcholine and other cholinergic agonists. Based on the specific cholinergic receptor affinity, these antagonists are classified as muscarinic or nicotinic. Anticholinergics interrupt parasympathetic innervations while sympathetic innervations remain uninterrupted. Muscarinic antagonists are also called 'muscarinic antagonists', 'antimuscarinics', or 'parasympatholytics'. Nicotinic...
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Updated: Aug 29, 2025

Isolation of F1-ATPase from the Parasitic Protist Trypanosoma brucei
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Phomoxanthone A Targets ATP Synthase.

Rameez Ali1, Sangram S Parelkar2, Paul R Thompson2

  • 1Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, 60 Prescott St., Worcester, MA 01609, USA.

Chemistry (Weinheim an Der Bergstrasse, Germany)
|September 9, 2022
PubMed
Summary
This summary is machine-generated.

Phomoxanthone A, an anti-cancer compound, was investigated to find its biological target. Researchers identified ATP synthase as a key target, showing it inhibits this enzyme in cells.

Keywords:
anticancerbiconjugationmicroscopynatural productphotoaffinity labelling

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Visualization of ATP Synthase Dimers in Mitochondria by Electron Cryo-tomography
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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Phomoxanthone A is a natural product with demonstrated anti-cancer properties.
  • The precise mechanism of action for Phomoxanthone A remains unelucidated.
  • Identifying the molecular target is crucial for understanding its anti-cancer effects.

Purpose of the Study:

  • To identify the biological target(s) of Phomoxanthone A.
  • To investigate the interaction between Phomoxanthone A and its potential targets.
  • To validate the identified target in cellular models.

Main Methods:

  • Affinity-based labeling using a Phomoxanthone A probe.
  • Chemoproteomics analysis employing Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).
  • Validation of target engagement in cultured cell lysates and live intact cells.

Main Results:

  • ATP synthase was identified as a likely direct target of Phomoxanthone A.
  • Mitochondrial ATP synthase activity was confirmed as a target in cellular assays.
  • Phomoxanthone A demonstrated significant inhibition of ATP synthase activity (60% at 260 μM).

Conclusions:

  • ATP synthase is a validated biological target of Phomoxanthone A.
  • The anti-cancer activity of Phomoxanthone A may be mediated through the inhibition of ATP synthase.
  • These findings provide a basis for further mechanistic studies and therapeutic development.