PDBsum entry: 1btk

Transferase

PDB id: 1btk

Contents

Protein chains

160 a.a. *

169 a.a. *

Metals

_NA ×2

_ZN ×2

Waters ×248

* Residue conservation analysis

PDB id:

1btk

Name:

Transferase

Title:

Ph domain and btk motif from bruton's tyrosine kinase mutant r28c

Structure:

Bruton's tyrosine kinase. Chain: a, b. Fragment: ph domain and btk motif. Synonym: bruton's agammaglobulinemia tyrosine kinase, btk. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell_line: bl21. Cell: b-lymphocyte. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.60Å R-factor: 0.231 R-free: 0.282

Authors:

M.Hyvonen,M.Saraste

Key ref:

M.Hyvönen and M.Saraste (1997). Structure of the PH domain and Btk motif from Bruton's tyrosine kinase: molecular explanations for X-linked agammaglobulinaemia. EMBO J, 16, 3396-3404. PubMed id: 9218782 DOI: 10.1093/emboj/16.12.3396

Date:

01-Jul-97 Release date: 17-Sep-97

Protein chain

Q06187  (BTK_HUMAN) -  Tyrosine-protein kinase BTK

Seq: 659 a.a.

Struc: 160 a.a.*

Protein chain

Q06187  (BTK_HUMAN) -  Tyrosine-protein kinase BTK

Seq: 659 a.a.

Struc: 169 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B: E.C.2.7.10.2 - Non-specific protein-tyrosine kinase.
• Reaction: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Biochemical function: protein binding (1 term)

reference

DOI no: 10.1093/emboj/16.12.3396

EMBO J 16:3396-3404 (1997)

PubMed id: 9218782

Structure of the PH domain and Btk motif from Bruton's tyrosine kinase: molecular explanations for X-linked agammaglobulinaemia.

M.Hyvönen, M.Saraste.

ABSTRACT

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.

Selected figure(s)

Figure 5.
Figure 5 Bindings site for inositol phosphates in PLC 1 and Btk PH domains. (A) Predicted binding site and the residues thought to be involved in Ins(1,3,4,5)P[4] binding in the Btk PH domain are shown in the upper panel. The corresponding area of the PLC 1 PH domain with residues in direct contact with Ins(1,4,5)P[4] is shown in the lower panel. The ball-and-stick models of the side chains are coloured according to atom types: carbons grey, nitrogens blue, oxygens red and sulfurs yellow. The view of the domains is along the C-terminal -helix, which is not visible in the figure. (B) Electrostatic polarization of Btk PH domain is shown using a surface representation of the Btk PH domain in the same orientation as in Figure 6A and B. The surface is coloured according to charge, with positive charge in blue and negative in red. The position of residues thought be involved in Ins(1,3,4,5)P[4] binding are marked on the surface. The figure was prepared using GRASP (Nicholls et al., 1991).

Figure 6.
Figure 6 Mutations and the predicted inositol-binding site in the Btk PH domain. (A) A ribbon representation of the Btk PH domain and Btk motif showing residues mutated in XLA patients as ball-and-stick models. Colouring is as in Figures 2 and 5A. (B) Same view of the molecule as in (A), showing the residues thought to form the Ins(1,3,4,5)P[4]-binding site as ball-and-stick models.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (1997, 16, 3396-3404) copyright 1997.

Figures were selected by an automated process.