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PDBsum entry 5d3y
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Lipid binding protein
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PDB id
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5d3y
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PDB id:
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| Name: |
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Lipid binding protein
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Title:
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Crystal structure of the p-rex1 ph domain with inositol-(1,3,4,5)- tetrakisphosphate bound
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Structure:
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Phosphatidylinositol 3,4,5-trisphosphate-dependent rac exchanger 1 protein. Chain: a, b. Fragment: unp residues 245-408. Synonym: ptdins(3,4,5)-dependent rac exchanger 1. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: prex1, kiaa1415. Expressed in: escherichia coli. Expression_system_taxid: 469008.
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Resolution:
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1.95Å
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R-factor:
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0.210
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R-free:
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0.258
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Authors:
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J.N.Cash,J.J.G.Tesmer
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Key ref:
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J.N.Cash
et al.
(2016).
Structural and Biochemical Characterization of the Catalytic Core of the Metastatic Factor P-Rex1 and Its Regulation by PtdIns(3,4,5)P3.
Structure,
24,
730-740.
PubMed id:
DOI:
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Date:
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06-Aug-15
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Release date:
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20-Apr-16
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PROCHECK
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Headers
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References
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Q8TCU6
(PREX1_HUMAN) -
Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 protein from Homo sapiens
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Seq:
Struc:
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1659 a.a.
136 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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DOI no:
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Structure
24:730-740
(2016)
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PubMed id:
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Structural and Biochemical Characterization of the Catalytic Core of the Metastatic Factor P-Rex1 and Its Regulation by PtdIns(3,4,5)P3.
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J.N.Cash,
E.M.Davis,
J.J.Tesmer.
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ABSTRACT
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Phosphatidylinositol 3,4,5-trisphosphate (PIP3)-dependent Rac exchanger 1
(P-Rex1) is a Rho guanine nucleotide exchange factor synergistically activated
by PIP3 and Gβγ 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.
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Links
