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

被引：178

作者：

Nowakowski, J

Cronin, CN

McRee, DE

Knuth, MW

Nelson, CG

Pavletich, NP

Rogers, J

Sang, BC

Scheibe, DN

Swanson, RV

Thompson, DA

机构：

[1] Syrrx Inc, San Diego, CA 92121 USA

[2] Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, New York, NY 10021 USA

来源：

STRUCTURE | 2002年 / 10卷 / 12期

关键词：

aurora; crystal structure; EphA2; FAK; protein kinase; nanovolume crystallography;

D O I：

10.1016/S0969-2126(02)00907-3

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 Angstrom 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.

引用

页码：1659 / 1667

页数：9

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