Related Experiment Video

Updated: Apr 15, 2026

Phosphoproteomic Strategy for Profiling Osmotic Stress Signaling in Arabidopsis
05:47

Phosphoproteomic Strategy for Profiling Osmotic Stress Signaling in Arabidopsis

Published on: June 25, 2020

5.8K

5,5'-Methylenedisalicylic Acid (MDSA) Modulates SarA/MgrA Phosphorylation by Targeting Ser/Thr Phosphatase Stp1

Weihao Zheng1, Yujie Liang, Hui Zhao

  • 1Key Lab of Chemical Genomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen 518055 (China).

Chembiochem : a European Journal of Chemical Biology
|March 27, 2015
PubMed

Insights

MDSA inhibits staphylococcal Ser/Thr phosphatase 1 (Stp1), enhancing SarA/MgrA phosphorylation. This discovery offers a new strategy for developing drugs to reduce Staphylococcus aureus virulence.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Drug Discovery

Background:

  • Key transcriptional regulators SarA, MgrA, and SarZ control Staphylococcus aureus virulence, drug resistance, and autolysis.
  • Eukaryotic-like Ser/Thr kinases/phosphatases (Stk1/Stp1) modulate these regulators and influence S. aureus virulence.
  • Stp1 is a potential drug target, as an stp1-deficient strain exhibits reduced virulence in mice.

Purpose of the Study:

  • To investigate the effect of MDSA, an MgrA inhibitor, on SarA/MgrA phosphorylation in S. aureus.
  • To determine if MDSA affects Stp1 activity.
  • To evaluate MDSA as a potential lead compound for anti-virulence drug development.

Main Methods:

  • Utilized Staphylococcus aureus strains.
  • Investigated the inhibitory effects of MDSA on Stp1 phosphatase activity.
  • Quantified SarA/MgrA phosphorylation levels.
  • Determined the IC50 of MDSA against Stp1.

Main Results:

  • MDSA inhibits Stp1 phosphatase activity in S. aureus.
  • MDSA treatment leads to enhanced phosphorylation of SarA and MgrA.
  • MDSA demonstrates potent inhibition of Stp1 (IC50 = 9.68 ± 0.52 μM), exceeding that of common phosphatase inhibitors.

Conclusions:

  • MDSA enhances SarA/MgrA phosphorylation by inhibiting Stp1 in S. aureus.
  • MDSA is a potent Stp1 inhibitor, suggesting its potential as a lead compound.
  • Targeting Stp1 with compounds like MDSA offers a promising avenue for developing novel anti-virulence strategies against Staphylococcus aureus.
Keywords:
Staphylococcus aureusStp1global regulatorsinhibitorsstructure-activity relationships

More Related Videos

MS2-Affinity Purification Coupled with RNA Sequencing in Gram-Positive Bacteria08:34

MS2-Affinity Purification Coupled with RNA Sequencing in Gram-Positive Bacteria

Published on: February 23, 2021

7.7K
Quantitative Methods to Study Protein Arginine Methyltransferase 1-9 Activity in Cells08:11

Quantitative Methods to Study Protein Arginine Methyltransferase 1-9 Activity in Cells

Published on: August 7, 2021

4.8K

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.5K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
14.2K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
19.6K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
9.5K
Phosphorylation01:02

Phosphorylation

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...
55.7K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.1K