PDBsum entry 3bbw

Transferase

PDB id: 3bbw

Contents

Protein chains

275 a.a. *

* Residue conservation analysis

PDB id:

3bbw

Name:

Transferase

Title:

Crystal structure of the erbb4 kinase in its inactive conformation

Structure:

Receptor tyrosine-protein kinase erbb-4. Chain: b, a. Synonym: p180erbb4, tyrosine kinase-type cell surface receptor her4. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: erbb4, her4. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.

Resolution:

4.00Å R-factor: 0.305 R-free: 0.354

Authors:

C.Qiu

Key ref:

C.Qiu et al. (2008). Mechanism of activation and inhibition of the HER4/ErbB4 kinase. Structure, 16, 460-467. PubMed id: 18334220 DOI: 10.1016/j.str.2007.12.016

Date:

11-Nov-07 Release date: 12-Feb-08

Protein chains

Q15303  (ERBB4_HUMAN) -  Receptor tyrosine-protein kinase erbB-4 from Homo sapiens

Seq: 1308 a.a.

Struc: 275 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.10.1 - receptor 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: 10.1016/j.str.2007.12.016

Structure 16:460-467 (2008)

PubMed id: 18334220

Mechanism of activation and inhibition of the HER4/ErbB4 kinase.

C.Qiu, M.K.Tarrant, S.H.Choi, A.Sathyamurthy, R.Bose, S.Banjade, A.Pal, W.G.Bornmann, M.A.Lemmon, P.A.Cole, D.J.Leahy.

ABSTRACT

HER4/ErbB4 is a ubiquitously expressed member of the EGF/ErbB family of receptor tyrosine kinases that is essential for normal development of the heart, nervous system, and mammary gland. We report here crystal structures of the ErbB4 kinase domain in active and lapatinib-inhibited forms. Active ErbB4 kinase adopts an asymmetric dimer conformation essentially identical to that observed to be important for activation of the EGF receptor/ErbB1 kinase. Mutagenesis studies of intact ErbB4 in Ba/F3 cells confirm the importance of this asymmetric dimer for activation of intact ErbB4. Lapatinib binds to an inactive form of the ErbB4 kinase in a mode equivalent to its interaction with the EGF receptor. All ErbB4 residues contacted by lapatinib are conserved in the EGF receptor and HER2/ErbB2, which lapatinib also targets. These results demonstrate that key elements of kinase activation and inhibition are conserved among ErbB family members.

Selected figure(s)

Figure 1.
Figure 1. Ribbon Diagrams of ErbB4 Kinase Structures
(A) The active conformation of the ErbB4 kinase. The activation loop is colored red.
(B) An inactive conformation of the ErbB4 kinase in complex with lapatinib, which is shown as a red stick model. The activation loop is disordered, but the loop termini are colored red.
(C) Superposition of the active and inactive conformations of the ErbB4 kinase.

Figure 2.
Figure 2. Superposition of the Asymmetric Dimers of EGFR and ErbB4 Kinase
The ErbB4 kinase subunits are colored blue and cyan. An EGFR dimer is colored light yellow. Only the single blue colored ErbB4 kinase subunit and corresponding EGFR subunit were included in the superposition.

The above figures are reprinted by permission from Cell Press: Structure (2008, 16, 460-467) copyright 2008.

Figures were selected by an automated process.