Allosteric modulation of a human protein kinase with monobodies

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 116; no. 28; pp. 13937 - 13942
• Main Authors: Zorba, Adelajda, Nguyen, Vy, Koide, Akiko, Hoemberger, Marc, Zheng, Yuejiao, Kutter, Steffen, Kim, Chansik, Koide, Shohei, Kern, Dorothee
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 09.07.2019
• Subjects: 60 APPLIED LIFE SCIENCES; Adenosine Triphosphate - chemistry; Adenosine Triphosphate - metabolism; allosteric drugs; Allosteric properties; Allosteric Regulation - genetics; allostery; Aurora A; Aurora Kinase A - antagonists & inhibitors; Aurora Kinase A - chemistry; Aurora Kinase A - genetics; Aurora Kinase B - antagonists & inhibitors; Aurora Kinase B - chemistry; Aurora Kinase B - genetics; Binding sites; Binding Sites - genetics; Biological Sciences; Carrier Proteins - chemistry; Carrier Proteins - genetics; Crystal structure; Crystallography, X-Ray; Drug delivery; Drug Design; Drug development; Fibronectin Type III Domain - genetics; Humans; kinase; Kinases; Modulation; Modulators; monobody; Physical Sciences; Protein Conformation; Protein kinase; Protein Kinase Inhibitors - chemistry; Protein Kinases - chemistry; Protein Kinases - genetics; science & technology - other topics; Selectivity; kinase; monobody; Aurora A; allosteric drugs; allostery

Despite being the subject of intense effort and scrutiny, kinases have proven to be consistently challenging targets in inhibitor drug design. A key obstacle has been promiscuity and consequent adverse effects of drugs targeting the ATP binding site. Here we introduce an approach to controlling kina...