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PDBsum entry 4ixp
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PDB id:
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Transferase
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Title:
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Crystal structure of maternal embryonic leucine zipper kinase (melk)
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Structure:
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Maternal embryonic leucine zipper kinase. Chain: a. Fragment: n-terminal. Synonym: hmelk, protein kinase eg3, peg3 kinase, protein kinase pk38, hpk38, tyrosine-protein kinase melk. Engineered: yes. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: melk, kiaa0175. Expressed in: escherichia coli. Expression_system_taxid: 469008.
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Resolution:
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2.75Å
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R-factor:
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0.204
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R-free:
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0.232
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Authors:
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L.S.Cao,J.Wang,Z.X.Wang,J.W.Wu
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Key ref:
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L.S.Cao
et al.
(2013).
Structural basis for the regulation of maternal embryonic leucine zipper kinase.
Plos One,
8,
e70031.
PubMed id:
DOI:
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Date:
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27-Jan-13
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Release date:
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11-Sep-13
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PROCHECK
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Headers
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References
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Q14680
(MELK_HUMAN) -
Maternal embryonic leucine zipper kinase from Homo sapiens
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Seq:
Struc:
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651 a.a.
334 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 2 residue positions (black
crosses)
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Enzyme class 2:
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E.C.2.7.10.2
- non-specific protein-tyrosine kinase.
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Reaction:
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L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H+
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L-tyrosyl-[protein]
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+
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ATP
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=
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O-phospho-L-tyrosyl-[protein]
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+
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ADP
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+
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H(+)
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Enzyme class 3:
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E.C.2.7.11.1
- non-specific serine/threonine protein kinase.
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Reaction:
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1.
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L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H+
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2.
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L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H+
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L-seryl-[protein]
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+
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ATP
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=
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O-phospho-L-seryl-[protein]
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+
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ADP
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+
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H(+)
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L-threonyl-[protein]
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+
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ATP
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=
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O-phospho-L-threonyl-[protein]
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+
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ADP
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+
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H(+)
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Note, where more than one E.C. class is given (as above), each may
correspond to a different protein domain or, in the case of polyprotein
precursors, to a different mature protein.
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Plos One
8:e70031
(2013)
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PubMed id:
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Structural basis for the regulation of maternal embryonic leucine zipper kinase.
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L.S.Cao,
J.Wang,
Y.Chen,
H.Deng,
Z.X.Wang,
J.W.Wu.
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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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Links
