The MST family is a subclass of mammalian serine/threonine kinases that are related to the yeast sterile-20 protein and are implicated in regulating cell growth and transformation. The MST3 protein contains a 300-residue catalytic domain and a 130-residue regulatory domain, which can be cleaved by caspase and activated by autophosphorylation, promoting apoptosis. Here, five crystal structures of the catalytic domain of MST3 are presented, including a complex with ADP and manganese, a unique cofactor preferred by the enzyme, and a complex with adenine. Similar to other protein kinases, the catalytic domain of MST3 folds into two lobes: the smaller N lobe forms the nucleotide-binding site and the larger C lobe recognizes the polypeptide substrate. The bound ADP and Mn2+ ions are covered by a glycine-rich loop and held in place by Asn149 and Asp162. A different orientation was observed for the ligand in the MST3-adenine complex. In the activation loop, the side chain of Thr178 is phosphorylated and is sandwiched by Arg143 and Arg176. Comparison of this structure with other similar kinase structures shows a 180° rotation of the loop, leading to activation of the enzyme. The well defined protein-ligand interactions also provide useful information for the design of potent inhibitors.
|頁（從 - 到）||145-154|
|期刊||Acta Crystallographica Section D: Biological Crystallography|
|出版狀態||已發佈 - 2010|
ASJC Scopus subject areas
- Structural Biology
Ko, T. P., Jeng, W. Y., Liu, C. I., Lai, M. D., Wu, C. L., Chang, W. J., Shr, H. L., Lu, T. J., & Wang, A. H. J. (2010). Structures of human MST3 kinase in complex with adenine, ADP and Mn 2+. Acta Crystallographica Section D: Biological Crystallography, 66(2), 145-154. https://doi.org/10.1107/S0907444909047507