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PDBsum entry 4ixp
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References listed in PDB file
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Key reference
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Title
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Structural basis for the regulation of maternal embryonic leucine zipper kinase.
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Authors
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L.S.Cao,
J.Wang,
Y.Chen,
H.Deng,
Z.X.Wang,
J.W.Wu.
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Ref.
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Plos One, 2013,
8,
e70031.
[DOI no: ]
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PubMed id
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Abstract
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MELK (maternal embryonic leucine zipper kinase), which is a member of the AMPK
(AMP-activated protein kinase)-related kinase family, plays important roles in
diverse cellular processes and has become a promising drug target for certain
cancers. However, the regulatory mechanism of MELK remains elusive. Here, we
report the crystal structure of a fragment of human MELK that contains the
kinase domain and ubiquitin-associated (UBA) domain. The UBA domain tightly
binds to the back of the kinase domain, which may contribute to the proper
conformation and activity of the kinase domain. Interestingly, the activation
segment in the kinase domain displays a unique conformation that contains an
intramolecular disulfide bond. The structural and biochemical analyses unravel
the molecular mechanisms for the autophosphorylation/activation of MELK and the
dependence of its catalytic activity on reducing agents. Thus, our results may
provide the basis for designing specific MELK inhibitors for cancer treatment.
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