PDBsum entry 1mqb

Transferase

PDB id: 1mqb

Contents

Protein chain

263 a.a. *

Ligands

ANP ×2

Waters ×66

* Residue conservation analysis

PDB id:

1mqb

Name:

Transferase

Title:

Crystal structure of ephrin a2 (epha2) receptor protein kinase

Structure:

Ephrin type-a receptor 2. Chain: a, b. Fragment: kinase domain. Synonym: epha2 receptor tyrosine kinase, tyrosine-protein kinase receptor eck, epithelial cell kinase. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: epha2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: hi5.

Resolution:

2.30Å R-factor: 0.236 R-free: 0.288

Authors:

J.Nowakowski,C.N.Cronin,D.E.Mcree,M.W.Knuth,C.Nelson,N.Pavletich, J.Rogers,B.C.Sang,D.N.Scheibe,R.V.Swanson,D.A.Thompson

Key ref:

J.Nowakowski et al. (2002). Structures of the cancer-related Aurora-A, FAK, and EphA2 protein kinases from nanovolume crystallography. Structure, 10, 1659-1667. PubMed id: 12467573 DOI: 10.1016/S0969-2126(02)00907-3

Date:

16-Sep-02 Release date: 16-Sep-03

Protein chains

P29317  (EPHA2_HUMAN) -  Ephrin type-A receptor 2 from Homo sapiens

Seq: 976 a.a.

Struc: 263 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⁺

L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] (Bound ligand (Het Group name = ANP) matches with 81.25% similarity) + ADP + H(+)

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

Added reference

DOI no: 10.1016/S0969-2126(02)00907-3

Structure 10:1659-1667 (2002)

PubMed id: 12467573

Structures of the cancer-related Aurora-A, FAK, and EphA2 protein kinases from nanovolume crystallography.

J.Nowakowski, C.N.Cronin, D.E.McRee, M.W.Knuth, C.G.Nelson, N.P.Pavletich, J.Rogers, B.C.Sang, D.N.Scheibe, R.V.Swanson, D.A.Thompson.

ABSTRACT

Protein kinases are important drug targets in human cancers, inflammation, and metabolic diseases. This report presents the structures of kinase domains for three cancer-associated protein kinases: ephrin receptor A2 (EphA2), focal adhesion kinase (FAK), and Aurora-A. The expression profiles of EphA2, FAK, and Aurora-A in carcinomas suggest that inhibitors of these kinases may have inherent potential as therapeutic agents. The structures were determined from crystals grown in nanovolume droplets, which produced high-resolution diffraction data at 1.7, 1.9, and 2.3 A for FAK, Aurora-A, and EphA2, respectively. The FAK and Aurora-A structures are the first determined within two unique subfamilies of human kinases, and all three structures provide new insights into kinase regulation and the design of selective inhibitors.

Selected figure(s)

Figure 5.
Figure 5. Stereo Diagrams of the ATP Binding Sites(A) Aurora-A ATP binding site. Carbon atoms, gray; oxygen atoms, red; nitrogen atoms, blue; phosphorus atoms, green. Water molecules and Mg2+ ions are represented by red and blue crosses, respectively.(B) FAK ATP binding site(C) EphA2 ATP binding site. The representative 2F[o] - F[c] electron density around the ATP has been computed at 1.9, 1.6, and 2.3 Å for Aurora-A, FAK, and EphA2, respectively. The density is contoured at 1 s (blue) and 4 s (red). The side chains of the residues that distinguish the structures of the ATP binding sites are shown with the dotted van der Waals surface. Hydrogen bonds between the protein and ATP are shown as dashed lines. The figure was prepared with Xfit [56].

The above figure is reprinted by permission from Cell Press: Structure (2002, 10, 1659-1667) copyright 2002.

Figure was selected by an automated process.