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3ko0

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Revision as of 19:34, 4 August 2016

Structure of the tfp-ca2+-bound activated form of the s100a4 Metastasis factor

Structural highlights

3ko0 is a 20 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	CAPL, MTS1, S100A4 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

S100A4, a member of the S100 family of Ca(2+)-binding proteins, regulates carcinoma cell motility via interactions with myosin-IIA. Numerous studies indicate that S100A4 is not simply a marker for metastatic disease, but rather has a direct role in metastatic progression. These observations suggest that S100A4 is an excellent target for therapeutic intervention. Using a unique biosensor-based assay, trifluoperazine (TFP) was identified as an inhibitor that disrupts the S100A4/myosin-IIA interaction. To examine the interaction of S100A4 with TFP, we determined the 2.3 A crystal structure of human Ca(2+)-S100A4 bound to TFP. Two TFP molecules bind within the hydrophobic target binding pocket of Ca(2+)-S100A4 with no significant conformational changes observed in the protein upon complex formation. NMR chemical shift perturbations are consistent with the crystal structure and demonstrate that TFP binds to the target binding cleft of S100A4 in solution. Remarkably, TFP binding results in the assembly of five Ca(2+)-S100A4/TFP dimers into a tightly packed pentameric ring. Within each pentamer most of the contacts between S100A4 dimers occurs through the TFP moieties. The Ca(2+)-S100A4/prochlorperazine (PCP) complex exhibits a similar pentameric assembly. Equilibrium sedimentation and cross-linking studies demonstrate the cooperative formation of a similarly sized S100A4/TFP oligomer in solution. Assays examining the ability of TFP to block S100A4-mediated disassembly of myosin-IIA filaments demonstrate that significant inhibition of S100A4 function occurs only at TFP concentrations that promote S100A4 oligomerization. Together these studies support a unique mode of inhibition in which phenothiazines disrupt the S100A4/myosin-IIA interaction by sequestering S100A4 via small molecule-induced oligomerization.

Phenothiazines inhibit S100A4 function by inducing protein oligomerization.,Malashkevich VN, Dulyaninova NG, Ramagopal UA, Liriano MA, Varney KM, Knight D, Brenowitz M, Weber DJ, Almo SC, Bresnick AR Proc Natl Acad Sci U S A. 2010 May 11;107(19):8605-10. Epub 2010 Apr 26. PMID:20421509^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Malashkevich VN, Dulyaninova NG, Ramagopal UA, Liriano MA, Varney KM, Knight D, Brenowitz M, Weber DJ, Almo SC, Bresnick AR. Phenothiazines inhibit S100A4 function by inducing protein oligomerization. Proc Natl Acad Sci U S A. 2010 May 11;107(19):8605-10. Epub 2010 Apr 26. PMID:20421509

1 Structural highlights
2 Evolutionary Conservation
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3ko0"

@@ Line 1: / Line 1: @@
 ==Structure of the tfp-ca2+-bound activated form of the s100a4 Metastasis factor==
 <StructureSection load='3ko0' size='340' side='right' caption='[[3ko0]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3ko0]] is a 20 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KO0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KO0 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3ko0]] is a 20 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KO0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KO0 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=TFP:10-[3-(4-METHYL-PIPERAZIN-1-YL)-PROPYL]-2-TRIFLUOROMETHYL-10H-PHENOTHIAZINE'>TFP</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CAPL, MTS1, S100A4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CAPL, MTS1, S100A4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3ko0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ko0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ko0 RCSB], [http://www.ebi.ac.uk/pdbsum/3ko0 PDBsum]</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=3ko0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ko0 OCA], [http://pdbe.org/3ko0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ko0 RCSB], [http://www.ebi.ac.uk/pdbsum/3ko0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ko0 ProSAT]</span></td></tr>
 </table>
 == Evolutionary Conservation ==
@@ Line 15: / Line 16: @@
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3ko0 ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 25: / Line 26: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3ko0" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 32: / Line 34: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Almo, S C]]
 [[Category: Bresnick, A R]]

3ko0

From Proteopedia

Revision as of 19:34, 4 August 2016

Structure of the tfp-ca2+-bound activated form of the s100a4 Metastasis factor

Structural highlights

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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