5f1m: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Crystal structure of Serine/threonine phosphatase Stp1 from Staphylococcus aureus== | |||
<StructureSection load='5f1m' size='340' side='right' caption='[[5f1m]], [[Resolution|resolution]] 2.32Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5f1m]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5F1M FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.16 3.1.3.16] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5f1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f1m OCA], [http://pdbe.org/5f1m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5f1m RCSB], [http://www.ebi.ac.uk/pdbsum/5f1m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5f1m ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The increasing threats of antibiotic resistance urge the need for developing new strategies against bacterial infections. Targeting eukaryotic-like Ser/Thr phosphatase Stp1-mediated virulence regulation represents a promising approach for combating staphylococcal infection yet to be explored. Here, we report the 2.32-A resolution crystal structure of Stp1. Stp1 binds an unexpected fourth metal ion, which is important for Stp1's enzymatic activity as demonstrated by amino acid substitution studies. Inspired by the structural details of Stp1, we identified a potent and selective Stp1 inhibitor, aurintricarboxylic acid (ATA). Transcriptome analysis and biochemical studies supported Stp1 as the target of ATA inhibition within the pathogen, preventing upregulation of virulence genes. Notably, ATA did not affect in vitro growth of Staphylococcus aureus, while simultaneously attenuating staphylococcal virulence in mice. Our findings demonstrate that ATA is a potent anti-virulence compound against staphylococcal infection, laying the foundation for further developing new scaffolds for Stp1-targeted small molecules. | |||
Structure-Based Identification of a Potent Inhibitor Targeting Stp1-Mediated Virulence Regulation in Staphylococcus aureus.,Zheng W, Cai X, Xie M, Liang Y, Wang T, Li Z Cell Chem Biol. 2016 Aug 18;23(8):1002-13. doi: 10.1016/j.chembiol.2016.06.014., Epub 2016 Aug 4. PMID:27499528<ref>PMID:27499528</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5f1m" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Serine/threonine protein phosphatase|Serine/threonine protein phosphatase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Phosphoprotein phosphatase]] | |||
[[Category: Li, Z G]] | |||
[[Category: Wang, T]] | |||
[[Category: Zheng, W H]] | |||
[[Category: Hydrolase]] | |||
[[Category: Serine/threonine phosphatase 1]] | |||
Revision as of 09:51, 10 September 2016
Crystal structure of Serine/threonine phosphatase Stp1 from Staphylococcus aureusCrystal structure of Serine/threonine phosphatase Stp1 from Staphylococcus aureus
Structural highlights
Publication Abstract from PubMedThe increasing threats of antibiotic resistance urge the need for developing new strategies against bacterial infections. Targeting eukaryotic-like Ser/Thr phosphatase Stp1-mediated virulence regulation represents a promising approach for combating staphylococcal infection yet to be explored. Here, we report the 2.32-A resolution crystal structure of Stp1. Stp1 binds an unexpected fourth metal ion, which is important for Stp1's enzymatic activity as demonstrated by amino acid substitution studies. Inspired by the structural details of Stp1, we identified a potent and selective Stp1 inhibitor, aurintricarboxylic acid (ATA). Transcriptome analysis and biochemical studies supported Stp1 as the target of ATA inhibition within the pathogen, preventing upregulation of virulence genes. Notably, ATA did not affect in vitro growth of Staphylococcus aureus, while simultaneously attenuating staphylococcal virulence in mice. Our findings demonstrate that ATA is a potent anti-virulence compound against staphylococcal infection, laying the foundation for further developing new scaffolds for Stp1-targeted small molecules. Structure-Based Identification of a Potent Inhibitor Targeting Stp1-Mediated Virulence Regulation in Staphylococcus aureus.,Zheng W, Cai X, Xie M, Liang Y, Wang T, Li Z Cell Chem Biol. 2016 Aug 18;23(8):1002-13. doi: 10.1016/j.chembiol.2016.06.014., Epub 2016 Aug 4. PMID:27499528[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||