1btk
From Proteopedia
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| - | [[Image:1btk.gif|left|200px]] | + | [[Image:1btk.gif|left|200px]] |
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| - | '''PH DOMAIN AND BTK MOTIF FROM BRUTON'S TYROSINE KINASE MUTANT R28C''' | + | {{Structure |
| + | |PDB= 1btk |SIZE=350|CAPTION= <scene name='initialview01'>1btk</scene>, resolution 1.6Å | ||
| + | |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=NA:SODIUM ION'>NA</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 R28C''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1BTK is a [ | + | 1BTK 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=1BTK OCA]. |
==Reference== | ==Reference== | ||
| - | Structure of the PH domain and Btk motif from Bruton's tyrosine kinase: molecular explanations for X-linked agammaglobulinaemia., Hyvonen M, Saraste M, EMBO J. 1997 Jun 16;16(12):3396-404. PMID:[http:// | + | Structure of the PH domain and Btk motif from Bruton's tyrosine kinase: molecular explanations for X-linked agammaglobulinaemia., Hyvonen M, Saraste M, EMBO J. 1997 Jun 16;16(12):3396-404. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9218782 9218782] |
[[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 10:15:39 2008'' |
Revision as of 08:15, 20 March 2008
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| , resolution 1.6Å | |||||||
|---|---|---|---|---|---|---|---|
| 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 R28C
Contents |
Overview
Bruton's tyrosine kinase (Btk) is an enzyme which is involved in maturation of B cells. It is a target for mutations causing X-linked agammaglobulinaemia (XLA) in man. We have determined the structure of the N-terminal part of Btk by X-ray crystallography at 1.6 A resolution. This part of the kinase contains a pleckstrin homology (PH) domain and a Btk motif. The structure of the PH domain is similar to those published previously: a seven-stranded bent beta-sheet with a C-terminal alpha-helix. Individual point mutations within the Btk PH domain which cause XLA can be classified as either structural or functional in the light of the three-dimensional structure and biochemical data. All functional mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids. It is likely that these mutations inactivate the Btk pathway in cell signalling by reducing its affinity for inositol phosphates, which causes a failure in translocation of the kinase to the cell membrane. A small number of signalling proteins contain a Btk motif that always follows a PH domain in the sequence. This small module has a novel fold which is held together by a zinc ion bound by three conserved cysteines and a histidine. The Btk motif packs against the second half of the beta-sheet of the PH domain, forming a close contact with it. Our structure opens up new ways to study the role of the PH domain and Btk motif in the cellular function of Btk and the molecular basis of its dysfunction in XLA patients.
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
1BTK is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of the PH domain and Btk motif from Bruton's tyrosine kinase: molecular explanations for X-linked agammaglobulinaemia., Hyvonen M, Saraste M, EMBO J. 1997 Jun 16;16(12):3396-404. PMID:9218782
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