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Redox process is crucial for inhibitory properties of aurintricarboxylic acid against activity of YopH: virulence factor of Yersinia pestis
- Source :
- Oncotarget
- Publication Year :
- 2015
-
Abstract
- YopH is a bacterial protein tyrosine phosphatase, which is essential for the viability and pathogenic virulence of the plague-causing Yersinia sp. bacteria. Inactivation of YopH activity would lead to the loss of bacterial pathogenicity. We have studied the inhibitory properties of aurintricarboxylic acid (ATA) against YopH phosphatase and found that at nanomolar concentrations ATA reversibly decreases the activity of YopH. Computational docking studies indicated that in all binding poses ATA binds in the YopH active site. Molecular dynamics simulations showed that in the predicted binding pose, ATA binds to the essential Cys403 and Arg409 residues in the active site and has a stronger binding affinity than the natural substrate (pTyr). The cyclic voltammetry experiments suggest that ATA reacts remarkably strongly with molecular oxygen. Additionally, the electrochemical reduction of ATA in the presence of a negative potential from -2.0 to 2.5 V generates a current signal, which is observed for hydrogen peroxide. Here we showed that ATA indicates a unique mechanism of YopH inactivation due to a redox process. We proposed that the potent inhibitory properties of ATA are a result of its strong binding in the YopH active site and in situ generation of hydrogen peroxide near catalytic cysteine residue.
- Subjects :
- Virulence Factors
Yersinia pestis
Phosphatase
Molecular Conformation
Protein tyrosine phosphatase
Plasma protein binding
Molecular Dynamics Simulation
ATA (aurintricarboxylic acid)
03 medical and health sciences
chemistry.chemical_compound
Aurintricarboxylic acid
Pathology Section
Humans
protein tyrosine phosphatase inhibitor
030304 developmental biology
0303 health sciences
Plague
biology
Molecular Structure
Virulence
030302 biochemistry & molecular biology
Aurintricarboxylic Acid
Active site
oxygen reduction/oxidation
YopH
biology.organism_classification
Research Paper: Pathology
virulence factor inhibition
Protein Structure, Tertiary
Kinetics
Oncology
chemistry
Biochemistry
Docking (molecular)
biology.protein
Protein Tyrosine Phosphatases
Oxidation-Reduction
Algorithms
Cysteine
Bacterial Outer Membrane Proteins
Protein Binding
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 6
- Issue :
- 21
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....0d34b6e86c71415661437fb93f725041