PDBsum entry 1k2p

Transferase

PDB id: 1k2p

Contents

Protein chains

258 a.a. *

* Residue conservation analysis

PDB id:

1k2p

Name:

Transferase

Title:

Crystal structure of bruton's tyrosine kinase domain

Structure:

Tyrosine-protein kinase btk. Chain: a, b. Fragment: bruton's tyrosine kinase domain. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Dimer (from PQS)

Resolution:

2.10Å R-factor: 0.221 R-free: 0.287

Authors:

C.Mao,M.Zhou,F.M.Uckun

Key ref:

C.Mao et al. (2001). Crystal structure of Bruton's tyrosine kinase domain suggests a novel pathway for activation and provides insights into the molecular basis of X-linked agammaglobulinemia. J Biol Chem, 276, 41435-41443. PubMed id: 11527964 DOI: 10.1074/jbc.M104828200

Date:

28-Sep-01 Release date: 26-Jun-02

Protein chains

Q06187  (BTK_HUMAN) -  Tyrosine-protein kinase BTK from Homo sapiens

Seq: 659 a.a.

Struc: 258 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.10.2 - non-specific protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

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

Added reference

DOI no: 10.1074/jbc.M104828200

J Biol Chem 276:41435-41443 (2001)

PubMed id: 11527964

Crystal structure of Bruton's tyrosine kinase domain suggests a novel pathway for activation and provides insights into the molecular basis of X-linked agammaglobulinemia.

C.Mao, M.Zhou, F.M.Uckun.

ABSTRACT

Bruton's tyrosine kinase is intimately involved in signal transduction pathways regulating survival, activation, proliferation, and differentiation of B lineage lymphoid cells. Mutations in the human btk gene are the cause of X-linked agammaglobulinemia, a male immune deficiency disorder characterized by a lack of mature, immunoglobulin-producing B lymphocytes. We have determined the x-ray crystal structure of the Bruton's tyrosine kinase kinase domain in its unphosphorylated state to a 2.1 A resolution. A comparison with the structures of other tyrosine kinases and a possible mechanism of activation unique to Bruton's tyrosine kinase are provided.

Selected figure(s)

Figure 2.
Fig. 2. Panel a, backbone positions of the A loop and C helix for BTK-KD (green), phospho-LCK (red), and c-SRC (white) are superimposed to illustrate their conformational differences and similarities. An AMP-PNP molecule ( pink) is present in the c-SRC crystal structure and was used to mark the location of active site. The side chains of Arg-544 and Tyr-551 in BTK and their equivalent residues in LCK and c-SRC on the A loop are shown. All coordinates were superimposed in CHAIN (28). Prepared using Insight II. Panel b, the noninhibitory (BTK) and inhibitory (IRK) conformations of the A loop are illustrated. Both crystal structures were first superimposed and shown separately in the same orientation with the A loops highlighted in rainbow tubes. Neither of the activation tyrosines is phosphorylated in the crystal structures. Prepared with GRASP (56).

Figure 3.
Fig. 3. Unique activation mechanism proposed based on the crystal structures of BTK-KD and phospho-LCK. Panel A, comparison of the superimposed BTK-KD (white backbones and multiple color side chains in stick model) and the phospho-LCK structures (gold backbones and red stick model side chains). The black lines indicate hydrogen bonds. Panel B, we propose that critical changes may occur when Arg-544 solely interacts with phosphotyrosine 551 upon phosphorylation and Arg-544 releases Glu-445, which subsequently takes part in ATP binding, which may be a critical component of catalysis. N-lobe, N-terminal lobe; C-lobe, C-terminal lobe.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2001, 276, 41435-41443) copyright 2001.

Figures were selected by an automated process.