2Z0P

Crystal structure of PH domain of Bruton's tyrosine kinase

Summary for 2Z0P

• Entry DOI: 10.2210/pdb2z0p/pdb
• Descriptor: Tyrosine-protein kinase BTK, ZINC ION, (2R)-3-{[(S)-{[(2S,3R,5S,6S)-2,6-DIHYDROXY-3,4,5-TRIS(PHOSPHONOOXY)CYCLOHEXYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-2-(1-HYDROXY BUTOXY)PROPYL BUTYRATE, ... (4 entities in total)
• Functional Keywords: ph domain, pip3c4, atp-binding, disease mutation, kinase, membrane, metal-binding, nucleotide-binding, nucleus, phosphorylation, sh2 domain, sh3 domain, transferase, tyrosine-protein kinase, zinc-finger, signaling protein, structural genomics, nppsfa, national project on protein structural and functional analyses, riken structural genomics/proteomics initiative, rsgi
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q06187
• Total number of polymer chains: 4
• Total formula weight: 83059.09

Authors

Murayama, K.,Kato-Murayama, M.,Mishima, C.,Shirouzu, M.,Yokoyama, S.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (deposition date: 2007-05-07, release date: 2008-05-13, Last modification date: 2023-11-01)

Primary citation

Murayama, K.,Kato-Murayama, M.,Mishima, C.,Akasaka, R.,Shirouzu, M.,Fukui, Y.,Yokoyama, S.
Crystal structure of the Bruton's tyrosine kinase PH domain with phosphatidylinositol
Biochem.Biophys.Res.Commun., 377:23-28, 2008

PubMed Abstract: Bruton's tyrosine kinase (Btk) of the Tec family possesses a Pleckstrin homology (PH) domain, which is responsible for plasma membrane targeting. In this study, the crystal structure of the Btk PH domain in complex with dibutylyl-phosphatidylinositol-3,4,5-triphosphate was determined. The structure revealed that the Btk PH domain forms a homodimer and that each molecule binds phosphatidylinositol in the binding pocket. The side chain of Lys18 within a Btk-specific insertion in the beta1-beta2 loop is able to form a hydrogen bond with the diacylglycerol moiety of phosphatidylinositol. The other Btk-specific insertion in the beta5-beta6 loop constitutes the dimerization interface. Thus, the modes of phosphatidylinositol recognition and Btk PH domain dimerization are distinct from those of other PH domains.

PubMed: 18809383
DOI: 10.1016/j.bbrc.2008.09.055

Experimental method

X-RAY DIFFRACTION (2.58 Å)