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PDBsum entry 3a7g
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References listed in PDB file
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Key reference
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Title
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Structures of human mst3 kinase in complex with adenine, Adp and mn2+.
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Authors
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T.P.Ko,
W.Y.Jeng,
C.I.Liu,
M.D.Lai,
C.L.Wu,
W.J.Chang,
H.L.Shr,
T.J.Lu,
A.H.Wang.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2010,
66,
145-154.
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PubMed id
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Abstract
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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.
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