3A7F

Human MST3 kinase

Summary for 3A7F

• Entry DOI: 10.2210/pdb3a7f/pdb
• Related: 3A7G 3A7H 3A7I 3A7J
• Descriptor: Serine/threonine kinase 24 (STE20 homolog, yeast) (2 entities in total)
• Functional Keywords: two-lobe protein kinase fold, atp-binding, kinase, nucleotide-binding, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 34336.19

Authors

Ko, T.P.,Jeng, W.Y.,Liu, C.I.,Lai, M.D.,Wang, A.H.J. (deposition date: 2009-09-26, release date: 2010-02-02, Last modification date: 2024-10-16)

Primary citation

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.
Structures of human MST3 kinase in complex with adenine, ADP and Mn2+.
Acta Crystallogr.,Sect.D, 66:145-154, 2010

PubMed Abstract: 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 Mn(2+) 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 degrees 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.

PubMed: 20124694
DOI: 10.1107/S0907444909047507

Experimental method

X-RAY DIFFRACTION (1.55 Å)