期刊
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
卷 1784, 期 1, 页码 48-55出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbapap.2007.09.016
关键词
MAP kinases; inhibitor binding; FXFP; sulindac; PD98059; X-ray crystallography
资金
- NIDDK NIH HHS [R01 DK046993-13, DK 46993, R01 DK046993] Funding Source: Medline
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK046993] Funding Source: NIH RePORTER
Map kinases are drug targets for autoimmune disease, cancer, and apoptosis-related diseases. Drug discovery efforts have developed MAP kinase inhibitors directed toward the ATP binding site and neighboring DFG-out site, both of which are targets for inhibitors of other protein kinases. On the other hand, MAP kinases have unique substrate and small molecule binding sites that could serve as inhibition sites. The substrate and processing enzyme D-motif binding site is present in all MAP kinases, and has many features of a good small molecule binding site. Further, the MAP kinase p38 alpha has a binding site near its C-terminus discovered in crystallographic studies. Finally, the MAP kinases ERK2 and p38 alpha have a second substrate binding site, the FXFP binding site that is exposed in active ERK2 and the D-motif peptide induced conformation of MAP kinases. Crystallographic evidence of these latter two binding sites is presented. (C) 2007 Elsevier B.V. All rights reserved.
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