Related Experiment Video
Updated: Feb 2, 2026
08:45
Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
Published on: July 17, 2020
6.6K
The Phosphohistidine Phosphatase SixA Targets a Phosphotransferase System
Jane E Schulte1, Mark Goulian2,3,4
1Graduate Group in Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Mbio
|November 29, 2018
Summary
SixA, a bacterial phosphohistidine phosphatase, regulates the nitrogen-related phosphotransferase system (PTSNtr) by removing phosphoryl groups from NPr. This study reveals a new role for SixA in modulating bacterial metabolic pathways.
Area of Science:
- Microbiology
- Biochemistry
- Molecular Biology
Background:
- Protein phosphorylation is a key regulatory mechanism in bacteria.
- Phosphohistidine phosphatases are rare, with SixA being the only known bacterial example.
- The nitrogen-related phosphotransferase system (PTSNtr) regulates metabolic processes via histidine phosphorylation.
Purpose of the Study:
- To investigate the ArcB-independent function of the phosphohistidine phosphatase SixA in *Escherichia coli*.
- To identify novel targets and roles of SixA beyond its interaction with ArcB.
- To elucidate the mechanism by which SixA modulates bacterial metabolic regulation.
Main Methods:
- Genetic screening for suppressors of *sixA* deletion growth defects.
- Analysis of various *E. coli* mutants.
- In vitro phosphorylation assays.
Main Results:
- SixA modulates the phosphorylation state of the nitrogen-related phosphotransferase system (PTSNtr).
- SixA acts on NPr, a component of the PTSNtr, to remove phosphoryl groups.
- This dephosphorylation activity is independent of the previously known target, ArcB.
Conclusions:
- SixA functions as a phosphohistidine phosphatase that dephosphorylates the PTSNtr pathway.
- This uncovers a novel regulatory mechanism for the PTSNtr, involving dephosphorylation.
- SixA's role suggests potential new targets for regulating bacterial metabolism.
Related Concept Videos
02:54Protein Kinases and Phosphatases
15.1K
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
15.1K
02:54Protein Kinases and Phosphatases
4.5K
4.5K
02:57Targeted Cancer Therapies
8.9K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
8.9K
01:26Targets for Drug Action: Overview
10.3K
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...
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...
10.3K
01:22Target Cell Response to Hormones
5.7K
Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
5.7K
01:02Phosphorylation
53.9K
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
53.9K