3i5s

From Proteopedia

(Difference between revisions)

Revision as of 09:36, 19 December 2018

Crystal structure of PI3K SH3

Structural highlights

3i5s is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3i5r
Gene:	GRB1, PIK3R1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT, TOPSAN

Function

[P85A_HUMAN] Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling.^[1] ^[2] ^[3]

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

Src homology 3 (SH3) domains are mediators of protein-protein interactions. They comprise approximately 60 amino acid residues and are found in many intracellular signaling proteins. Here, we present the crystal structure of the SH3 domain from phosphatidylinositol 3-kinase (PI3K) in complex with the 12-residue proline-rich peptide PD1R (HSKRPLPPLPSL). The crystal structure of the PI3K SH3-PD1R complex at a resolution of 1.7 A reveals type I ligand orientation of the bound peptide with an extended conformation where the central portion forms a left-handed type II polyproline (PPII) helix. The overall structure of the SH3 domain shows minimal changes on ligand binding. In addition, we also attempted crystallization with another peptide ligand (PD1) where the residue at anchor position P(-3) is a tyrosine. The crystals obtained did not contain the PD1 ligand; instead, the ligand binding site is partially occupied by residues Arg18 and Trp55 from the symmetry-related PI3K SH3 molecule. Considering these crystal structures of PI3K SH3 together with published reports, we provide a comparative analysis of protein-ligand interactions that has helped us identify the individual residues which play an important role in defining target specificity.

Structural studies of the phosphatidylinositol 3-kinase (PI3K) SH3 domain in complex with a peptide ligand: role of the anchor residue in ligand binding.,Batra-Safferling R, Granzin J, Modder S, Hoffmann S, Willbold D Biol Chem. 2010 Jan;391(1):33-42. PMID:19919182^[4]

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

References

↑ Vainikka S, Joukov V, Wennstrom S, Bergman M, Pelicci PG, Alitalo K. Signal transduction by fibroblast growth factor receptor-4 (FGFR-4). Comparison with FGFR-1. J Biol Chem. 1994 Jul 15;269(28):18320-6. PMID:7518429
↑ Miled N, Yan Y, Hon WC, Perisic O, Zvelebil M, Inbar Y, Schneidman-Duhovny D, Wolfson HJ, Backer JM, Williams RL. Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit. Science. 2007 Jul 13;317(5835):239-42. PMID:17626883 doi:317/5835/239
↑ Mandelker D, Gabelli SB, Schmidt-Kittler O, Zhu J, Cheong I, Huang CH, Kinzler KW, Vogelstein B, Amzel LM. A frequent kinase domain mutation that changes the interaction between PI3Kalpha and the membrane. Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):16996-7001. Epub 2009 Sep 23. PMID:19805105
↑ Batra-Safferling R, Granzin J, Modder S, Hoffmann S, Willbold D. Structural studies of the phosphatidylinositol 3-kinase (PI3K) SH3 domain in complex with a peptide ligand: role of the anchor residue in ligand binding. Biol Chem. 2010 Jan;391(1):33-42. PMID:19919182 doi:10.1515/BC.2010.003

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3i5s"

@@ Line 1: / Line 1: @@
 ==Crystal structure of PI3K SH3==
 <StructureSection load='3i5s' size='340' side='right' caption='[[3i5s]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3i5r|3i5r]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GRB1, PIK3R1 ([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=3i5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i5s OCA], [http://pdbe.org/3i5s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3i5s RCSB], [http://www.ebi.ac.uk/pdbsum/3i5s PDBsum], [http://www.topsan.org/Proteins/CESG/3i5s TOPSAN]</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=3i5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i5s OCA], [http://pdbe.org/3i5s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3i5s RCSB], [http://www.ebi.ac.uk/pdbsum/3i5s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3i5s ProSAT], [http://www.topsan.org/Proteins/CESG/3i5s TOPSAN]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i5/3i5s_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i5/3i5s_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 42: / Line 43: @@
 [[Category: Modder, S]]
 [[Category: Willbold, D]]
+[[Category: Alternative splicing]]
 [[Category: Disease mutation]]
 [[Category: Host-virus interaction]]
 [[Category: Phosphoprotein]]
+[[Category: Polymorphism]]
 [[Category: Protein binding]]
 [[Category: Sh2 domain]]
 [[Category: Sh3 domain]]
+[[Category: Ubl conjugation]]

3i5s

From Proteopedia

Revision as of 09:36, 19 December 2018

Crystal structure of PI3K SH3

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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