1b55

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[[Image:1b55.gif|left|200px]]
[[Image:1b55.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 1b55 |SIZE=350|CAPTION= <scene name='initialview01'>1b55</scene>, resolution 2.4&Aring;
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The line below this paragraph, containing "STRUCTURE_1b55", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=4IP:INOSITOL-(1,3,4,5)-TETRAKISPHOSPHATE'>4IP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE=
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|DOMAIN=
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{{STRUCTURE_1b55| PDB=1b55 | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1b55 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1b55 OCA], [http://www.ebi.ac.uk/pdbsum/1b55 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1b55 RCSB]</span>
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}}
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'''PH DOMAIN FROM BRUTON'S TYROSINE KINASE IN COMPLEX WITH INOSITOL 1,3,4,5-TETRAKISPHOSPHATE'''
'''PH DOMAIN FROM BRUTON'S TYROSINE KINASE IN COMPLEX WITH INOSITOL 1,3,4,5-TETRAKISPHOSPHATE'''
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[[Category: Saraste, M.]]
[[Category: Saraste, M.]]
[[Category: Surdo, P Lo.]]
[[Category: Surdo, P Lo.]]
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[[Category: btk motif]]
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[[Category: Btk motif]]
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[[Category: inositol 1,3,4,5-tetrakisphosphate]]
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[[Category: Inositol 1,3,4,5-tetrakisphosphate]]
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[[Category: ph domain]]
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[[Category: Ph domain]]
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[[Category: transferase]]
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[[Category: Transferase]]
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[[Category: tyrosine-protein kinase]]
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[[Category: Tyrosine-protein kinase]]
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[[Category: x-linked agammaglobulinemia]]
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[[Category: X-linked agammaglobulinemia]]
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[[Category: zinc binding]]
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[[Category: Zinc binding]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 11:05:08 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 18:53:48 2008''
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Revision as of 08:05, 2 May 2008

Image:1b55.gif

Template:STRUCTURE 1b55

PH DOMAIN FROM BRUTON'S TYROSINE KINASE IN COMPLEX WITH INOSITOL 1,3,4,5-TETRAKISPHOSPHATE


Overview

BACKGROUND: The activity of Bruton's tyrosine kinase (Btk) is important for the maturation of B cells. A variety of point mutations in this enzyme result in a severe human immunodeficiency known as X-linked agammaglobulinemia (XLA). Btk contains a pleckstrin-homology (PH) domain that specifically binds phosphatidylinositol 3,4,5-trisphosphate and, hence, responds to signalling via phosphatidylinositol 3-kinase. Point mutations in the PH domain might abolish membrane binding, preventing signalling via Btk. RESULTS: We have determined the crystal structures of the wild-type PH domain and a gain-of-function mutant E41K in complex with D-myo-inositol 1,3,4,5-tetra-kisphosphate (Ins (1,3,4,5)P4). The inositol Ins (1,3,4,5)P4 binds to a site that is similar to the inositol 1,4,5-trisphosphate binding site in the PH domain of phospholipase C-delta. A second Ins (1,3,4,5)P4 molecule is associated with the domain of the E41K mutant, suggesting a mechanism for its constitutive interaction with membrane. The affinities of Ins (1,3,4,5)P4 to the wild type (Kd = 40 nM), and several XLA-causing mutants have been measured using isothermal titration calorimetry. CONCLUSIONS: Our data provide an explanation for the specificity and high affinity of the interaction with phosphatidylinositol 3,4,5-trisphosphate and lead to a classification of the XLA mutations that reside in the Btk PH domain. Mis-sense mutations that do not simply destabilize the PH fold either directly affect the interaction with the phosphates of the lipid head group or change electrostatic properties of the lipid-binding site. One point mutation (Q127H) cannot be explained by these facts, suggesting that the PH domain of Btk carries an additional function such as interaction with a Galpha protein.

About this Structure

1B55 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structure of the PH domain from Bruton's tyrosine kinase in complex with inositol 1,3,4,5-tetrakisphosphate., Baraldi E, Djinovic Carugo K, Hyvonen M, Surdo PL, Riley AM, Potter BV, O'Brien R, Ladbury JE, Saraste M, Structure. 1999 Apr 15;7(4):449-60. PMID:10196129 Page seeded by OCA on Fri May 2 11:05:08 2008

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