Crystal structure of aurora-2, an oncogenic serine/threonine kinase.
Aurora-2 is a key member of a closely related subgroup of serine/threonine kinases that plays important roles in the completion of essential mitotic events. Aurora-2 is oncogenic and amplified in various human cancers and could be an important therapeutic target for inhibitory molecules that would disrupt the cell cycle and block proliferation. We report the first crystal structure of Aurora-2 kinase in complex with adenosine. Analysis of residues in the active site suggests differences with structurally and biologically related protein kinases. The activation loop, which contains residues specific to the Aurora family of kinases, has a unique conformation. These results provide valuable insight into the design of selective and highly potent ATP-competitive inhibitors of the Aurora kinases.
Cheetham
Graham M T
GM
Vertex Pharmaceuticals (Europe) Ltd., 88 Milton Park, Abingdon, Oxfordshire OX14 4RY, United Kingdom. cheetham@vpharm.com
Knegtel
Ronald M A
RM
Coll
Joyce T
JT
Renwick
Suzanne B
SB
Swenson
Lora
L
Weber
Peter
P
Lippke
Judith A
JA
Austen
Douglas A
DA
D064127:Aurora Kinases; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000201:enzymology; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D017384:Sequence Deletion
D011994:Recombinant Proteins; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases