Structural Comparison of Human Mammalian Ste20-Like Kinases

摘要: Background The serine/threonine mammalian Ste-20 like kinases (MSTs) are key regulators of apoptosis, cellular proliferation as well polarization. Deregulation MSTs has been associated with disease progression in prostate and colorectal cancer. The four human regulated differently by C-terminal regions flanking the catalytic domains. Principal Findings We have determined crystal structure kinase domain MST4 complex an ATP-mimetic inhibitor. This is first inactive conformation a member MST family. Comparison active structures MST3 MST1 revealed dimeric association suggesting activation loop exchanged mechanism auto-activation. Together homology model MST2 we provide comparative analysis domains for all members family. Significance identified new structural features ATP binding pocket also defined autophosphorylation. Both may be further explored inhibitors design. Enhanced version This article can viewed enhanced which text integrated interactive 3D representations animated transitions. Please note that web plugin required to access this functionality. Instructions installation use available Text S1.