PDBsum entry 2qol

Transferase

PDB id: 2qol

Contents

Protein chain

273 a.a. *

Waters ×422

* Residue conservation analysis

PDB id:

2qol

Name:

Transferase

Title:

Human epha3 kinase and juxtamembrane region, y596:y602:s768g triple mutant

Structure:

Ephrin receptor. Chain: a. Fragment: juxtamembrane segment and kinase domain: residues 577-947. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Tissue: placenta. Gene: epha3. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.07Å R-factor: 0.196 R-free: 0.211

Authors:

T.Davis,J.R.Walker,E.M.Newman,F.Mackenzie,C.Butler-Cole,J.Weigelt, M.Sundstrom,C.H.Arrowsmith,A.M.Edwards,A.Bochkarev,S.Dhe-Paganon, Structural Genomics Consortium (Sgc)

Key ref:

T.L.Davis et al. (2008). Autoregulation by the juxtamembrane region of the human ephrin receptor tyrosine kinase A3 (EphA3). Structure, 16, 873-884. PubMed id: 18547520 DOI: 10.1016/j.str.2008.03.008

Date:

20-Jul-07 Release date: 28-Aug-07

Protein chain

P29320  (EPHA3_HUMAN) -  Ephrin type-A receptor 3 from Homo sapiens

Seq: 983 a.a.

Struc: 273 a.a.*

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

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.2008.03.008

Structure 16:873-884 (2008)

PubMed id: 18547520

Autoregulation by the juxtamembrane region of the human ephrin receptor tyrosine kinase A3 (EphA3).

T.L.Davis, J.R.Walker, P.Loppnau, C.Butler-Cole, A.Allali-Hassani, S.Dhe-Paganon.

ABSTRACT

Ephrin receptors (Eph) affect cell shape and movement, unlike other receptor tyrosine kinases that directly affect proliferative pathways. The kinase domain of EphA3 is activated by ephrin binding and receptor oligomerization. This activation is associated with two tyrosines in the juxtamembrane region; these tyrosines are sites of autophosphorylation and interact with the active site of the kinase to modulate activity. This allosteric event has important implications both in terms of understanding signal transduction pathways mediated by Eph kinases as well as discovering specific therapeutic ligands for receptor kinases. In order to provide further details of the molecular mechanism through which the unphosphorylated juxtamembrane region blocks catalysis, we studied wild-type and site-specific mutants in detail. High-resolution structures of multiple states of EphA3 kinase with and without the juxtamembrane segment allowed us to map the coupled pathway of residues that connect the juxtamembrane segment, the activation loop, and the catalytic residues of the kinase domain. This highly conserved set of residues likely delineates a molecular recognition pathway for most of the Eph RTKs, helping to characterize the dynamic nature of these physiologically important enzymes.

Selected figure(s)

Figure 2.
Figure 2. Overall Structure of EphA3 Kinase
All molecular graphics figures were generated using PyMOL unless noted.
(A) Cartoon representation of the EphA3 JMKIN base ANP structure. The structure is shown in forest green and in cartoon representation. Secondary structure elements and regions discussed in the test are labeled. Regions of disorder are indicated with dashed lines. This structure was chosen because it represents the highest degree of order modeled for all the EphA3 structures.
(B) Ribbon representation of JMKIN base ANP overlaid with EphB2 in pink (1JPA). Alignment over all atoms yields an rmsd of less than 1Å for all structures; key regions of structural difference occur in the N-terminal lobe, centered on the JMS and the AL, along with slight differences in the β1-G loop-β2 region.

Figure 4.
Figure 4. The Linker Between the Kinase and SAM Domains Binds into a Complementary Pocket on the C-terminal Lobe of the Kinase Domain
An electrostatic surface was generated using APBS (Baker et al., 2001) using a gradient from −10 to 10 keT. Shown in cartoon and stick representation is the model for KIN ANP in firebrick red; this model contains the most ordered linker region comprising residues 885–906. Highlighted is the complementary surface made up by Tyr841, Leu901, and Leu903.

The above figures are reprinted by permission from Cell Press: Structure (2008, 16, 873-884) copyright 2008.

Figures were selected by an automated process.