PDBsum entry 3zfx

Transferase

PDB id: 3zfx

Contents

Protein chains

267 a.a.

254 a.a.

Ligands

SO4

Waters ×134

PDB id:

3zfx

Name:

Transferase

Title:

Crystal structure of ephb1

Structure:

Ephrin type-b receptor 1. Chain: a, b, c, d, e, f, g, h, i. Fragment: kinase domain. Synonym: 2.7.10.1, elk, eph tyrosine kinase 2, eph-like kinase 6, ek6, hek6, neuronally-expressed eph-related tyrosine kinase, net, tyrosine-protein kinase receptor eph-2, ephb1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: star.

Resolution:

2.50Å R-factor: 0.190 R-free: 0.217

Authors:

J.E.Debreczeni,R.Overman,C.Truman,M.Mcalister,T.K.Attwood

Key ref:

R.C.Overman et al. (2014). Completing the structural family portrait of the human EphB tyrosine kinase domains. Protein Sci, 23, 627-638. PubMed id: 24677421 DOI: 10.1002/pro.2445

Date:

12-Dec-12 Release date: 08-Jan-14

Protein chains

P54762  (EPHB1_HUMAN) -  Ephrin type-B receptor 1 from Homo sapiens

Seq: 984 a.a.

Struc: 267 a.a.

Protein chains

P54762  (EPHB1_HUMAN) -  Ephrin type-B receptor 1 from Homo sapiens

Seq: 984 a.a.

Struc: 254 a.a.

Enzyme reactions

• Enzyme class: Chains A, B, C, D, E, F, G, H, I: 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: 10.1002/pro.2445

Protein Sci 23:627-638 (2014)

PubMed id: 24677421

Completing the structural family portrait of the human EphB tyrosine kinase domains.

R.C.Overman, J.E.Debreczeni, C.M.Truman, M.S.McAlister, T.K.Attwood.

ABSTRACT

The EphB receptors have key roles in cell morphology, adhesion, migration and invasion, and their aberrant action has been linked with the development and progression of many different tumor types. Their conflicting expression patterns in cancer tissues, combined with their high sequence and structural identity, present interesting challenges to those seeking to develop selective therapeutic molecules targeting this large receptor family. Here, we present the first structure of the EphB1 tyrosine kinase domain determined by X-ray crystallography to 2.5Å. Our comparative crystalisation analysis of the human EphB family kinases has also yielded new crystal forms of the human EphB2 and EphB4 catalytic domains. Unable to crystallize the wild-type EphB3 kinase domain, we used rational engineering (based on our new structures of EphB1, EphB2, and EphB4) to identify a single point mutation which facilitated its crystallization and structure determination to 2.2 Å. This mutation also improved the soluble recombinant yield of this kinase within Escherichia coli, and increased both its intrinsic stability and catalytic turnover, without affecting its ligand-binding profile. The partial ordering of the activation loop in the EphB3 structure alludes to a potential cis-phosphorylation mechanism for the EphB kinases. With the kinase domain structures of all four catalytically competent human EphB receptors now determined, a picture begins to emerge of possible opportunities to produce EphB isozyme-selective kinase inhibitors for mechanistic studies and therapeutic applications.