 |
PDBsum entry 1mqb
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structures of the cancer-Related aurora-A, Fak, And epha2 protein kinases from nanovolume crystallography.
|
|
|
Authors
|
|
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.
|
|
|
Ref.
|
|
Structure, 2002,
10,
1659-1667.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
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.
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
