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5d3x

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Revision as of 04:37, 21 September 2017

Crystal Structure of the P-Rex1 PH domain with Inositol-(1,3,4,5)-Tetrakisphosphate Bound

Structural highlights

5d3x is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	5d27, 5d3v, 5d3w, 5d3y
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PREX1_HUMAN] Functions as a RAC guanine nucleotide exchange factor (GEF), which activates the Rac proteins by exchanging bound GDP for free GTP. Its activity is synergistically activated by phosphatidylinositol 3,4,5-trisphosphate and the beta gamma subunits of heterotrimeric G protein. May function downstream of heterotrimeric G proteins in neutrophils.

Publication Abstract from PubMed

Phosphatidylinositol 3,4,5-trisphosphate (PIP3)-dependent Rac exchanger 1 (P-Rex1) is a Rho guanine nucleotide exchange factor synergistically activated by PIP3 and Gbetagamma that plays an important role in the metastasis of breast, prostate, and skin cancer, making it an attractive therapeutic target. However, the molecular mechanisms behind P-Rex1 regulation are poorly understood. We determined structures of the P-Rex1 pleckstrin homology (PH) domain bound to the headgroup of PIP3 and resolved that PIP3 binding to the PH domain is required for P-Rex1 activity in cells but not for membrane localization, which points to an allosteric activation mechanism by PIP3. We also determined structures of the P-Rex1 tandem Dbl homology/PH domains in complexes with two of its substrate GTPases, Rac1 and Cdc42. Collectively, this study provides important molecular insights into P-Rex1 regulation and tools for targeting the PIP3-binding pocket of P-Rex1 with a new generation of cancer chemotherapeutic agents.

Structural and Biochemical Characterization of the Catalytic Core of the Metastatic Factor P-Rex1 and Its Regulation by PtdIns(3,4,5)P3.,Cash JN, Davis EM, Tesmer JJ Structure. 2016 May 3;24(5):730-40. doi: 10.1016/j.str.2016.02.022. Epub 2016 Apr, 14. PMID:27150042^[1]

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

References

↑ Cash JN, Davis EM, Tesmer JJ. Structural and Biochemical Characterization of the Catalytic Core of the Metastatic Factor P-Rex1 and Its Regulation by PtdIns(3,4,5)P3. Structure. 2016 May 3;24(5):730-40. doi: 10.1016/j.str.2016.02.022. Epub 2016 Apr, 14. PMID:27150042 doi:http://dx.doi.org/10.1016/j.str.2016.02.022

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5d3x"

@@ Line 6: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4IP:INOSITOL-(1,3,4,5)-TETRAKISPHOSPHATE'>4IP</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5d27|5d27]], [[5d3v|5d3v]], [[5d3w|5d3w]], [[5d3y|5d3y]]</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=5d3x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d3x OCA], [http://pdbe.org/5d3x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5d3x RCSB], [http://www.ebi.ac.uk/pdbsum/5d3x 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=5d3x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d3x OCA], [http://pdbe.org/5d3x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5d3x RCSB], [http://www.ebi.ac.uk/pdbsum/5d3x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5d3x ProSAT]</span></td></tr>
 </table>
 == Function ==

5d3x

From Proteopedia

Revision as of 04:37, 21 September 2017

Crystal Structure of the P-Rex1 PH domain with Inositol-(1,3,4,5)-Tetrakisphosphate Bound

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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