Structures of human MST3 kinase in complex with adenine, ADP and Mn 2+

Tzu Ping Ko, Wen-Yih Jeng, Chia I. Liu, Ming-Derg Lai, Chun Lan Wu, Wei Jung Chang, Hui Lin Shr, Te Jung Lu, Andrew H.J. Wang

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)145-154
Number of pages10
JournalActa Crystallographica Section D: Biological Crystallography
Volume66
Issue number2
DOIs
Publication statusPublished - 2010 Feb 17

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Adenine
Adenosine Diphosphate
Catalytic Domain
Phosphotransferases
Ligands
Proteins
Enzyme Activation
Protein-Serine-Threonine Kinases
Coenzymes
Manganese
Caspases
Glycine
Protein Kinases
Nucleotides
Yeasts
Binding Sites
Ions
Apoptosis
Peptides
Growth

All Science Journal Classification (ASJC) codes

  • Structural Biology

Cite this

Ko, Tzu Ping ; Jeng, Wen-Yih ; Liu, Chia I. ; Lai, Ming-Derg ; Wu, Chun Lan ; Chang, Wei Jung ; Shr, Hui Lin ; Lu, Te Jung ; Wang, Andrew H.J. / Structures of human MST3 kinase in complex with adenine, ADP and Mn 2+. In: Acta Crystallographica Section D: Biological Crystallography. 2010 ; Vol. 66, No. 2. pp. 145-154.
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Structures of human MST3 kinase in complex with adenine, ADP and Mn 2+. / Ko, Tzu Ping; Jeng, Wen-Yih; Liu, Chia I.; Lai, Ming-Derg; Wu, Chun Lan; Chang, Wei Jung; Shr, Hui Lin; Lu, Te Jung; Wang, Andrew H.J.

In: Acta Crystallographica Section D: Biological Crystallography, Vol. 66, No. 2, 17.02.2010, p. 145-154.

Research output: Contribution to journalArticle

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