1bwn
From Proteopedia
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| - | [[Image:1bwn.gif|left|200px]] | + | [[Image:1bwn.gif|left|200px]] |
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| - | '''PH DOMAIN AND BTK MOTIF FROM BRUTON'S TYROSINE KINASE MUTANT E41K IN COMPLEX WITH INS(1,3,4,5)P4''' | + | {{Structure |
| + | |PDB= 1bwn |SIZE=350|CAPTION= <scene name='initialview01'>1bwn</scene>, resolution 2.1Å | ||
| + | |SITE= <scene name='pdbsite=ZN1:Zn+Binding+Site+In+The+Btk+Motif,+Chain+A'>ZN1</scene> and <scene name='pdbsite=ZN2:Zn+Binding+Site+In+The+Btk+Motif,+Chain+B'>ZN2</scene> | ||
| + | |LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> and <scene name='pdbligand=4IP:INOSITOL-(1,3,4,5)-TETRAKISPHOSPHATE'>4IP</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Transferred_entry:_2.7.10.1_and_2.7.10.2 Transferred entry: 2.7.10.1 and 2.7.10.2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.112 2.7.1.112] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''PH DOMAIN AND BTK MOTIF FROM BRUTON'S TYROSINE KINASE MUTANT E41K IN COMPLEX WITH INS(1,3,4,5)P4''' | ||
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==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1BWN is a [ | + | 1BWN is a [[Single protein]] structure of 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=1BWN OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/10196129 10196129] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: zinc binding]] | [[Category: zinc binding]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:16:42 2008'' |
Revision as of 08:16, 20 March 2008
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| , resolution 2.1Å | |||||||
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| Sites: | and | ||||||
| Ligands: | and | ||||||
| Activity: | Transferred entry: 2.7.10.1 and 2.7.10.2, with EC number 2.7.1.112 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
PH DOMAIN AND BTK MOTIF FROM BRUTON'S TYROSINE KINASE MUTANT E41K IN COMPLEX WITH INS(1,3,4,5)P4
Contents |
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.
Disease
Known diseases associated with this structure: Agammaglobulinemia, type 1, X-linked OMIM:[300300], XLA and isolated growth hormone deficiency OMIM:[300300]
About this Structure
1BWN 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 Thu Mar 20 10:16:42 2008
Categories: Homo sapiens | Single protein | Transferred entry: 2 7.10 1 and 2 7.10 2 | Baraldi, E. | Carugo, K Djinovic. | Hyvoenen, M. | Potter, B. | Riley, A. | Saraste, M. | Surdo, P Lo. | 4IP | ZN | 3 | 4 | 5)-tetrakisphosphate | Btk motif | Inositol-(1 | Ph domain | Transferase | Tyrosine-protein kinase | X-linked agammaglobulinemia | Zinc binding
