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PDBsum entry 1zmv
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Signaling protein,transferase
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PDB id
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1zmv
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References listed in PDB file
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Key reference
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Title
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Structure of the catalytic and ubiquitin-Associated domains of the protein kinase mark/par-1.
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Authors
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S.Panneerselvam,
A.Marx,
E.M.Mandelkow,
E.Mandelkow.
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Ref.
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Structure, 2006,
14,
173-183.
[DOI no: ]
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PubMed id
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Abstract
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The Ser/Thr kinase MARK2 phosphorylates tau protein at sites that cause
detachment from microtubules in Alzheimer neurofibrillary degeneration. Homologs
of MARK2 include Par-1 in C. elegans and Drosophila, which generates embryonic
polarity. We report the X-ray structure of the catalytic and
ubiquitin-associated domains (UBA) of human MARK2. The activity was altered by
mutations in the ATP binding site and/or activation loop. The catalytic domain
shows the small and large lobes typical of kinases. The substrate cleft is in an
inactive, open conformation in the inactivated and the wild-type structure. The
UBA domain is attached via a taut linker to the large lobe of the kinase domain
and leans against a hydrophobic patch on the small lobe. The UBA structure is
unusual because the orientation of its third helix is inverted, relative to
previous structures. Possible implications of the structure for the regulation
of kinase activity are discussed.
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Figure 7.
Figure 7. Common Docking Domain and ED Site of MAP Kinases
Compared to MARK2
The structures of (A) MARK2 and (B) ERK2
(PDB code 2ERK [Canagarajah et al., 1997]) are shown in the same
orientations after least-squares superposition of 35 residues
from helix E to the catalytic loop. The common docking domain
(CD, in red) according to Tanoue and Nishida (2003) is C
terminal to the kinase domain and corresponds in MARK to the
first half of the tether connecting the kinase domain to the UBA
domain (residues  vert,
similar 305-315). The C-terminal extensions following the CD
domain (linker and UBA domain in MARK2) are shown in purple.
Characteristic for the CD domain is a cluster of negatively
charged residues exposed to the surface, located in a bulge at
the end of the catalytic domain (stick model representation).
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2006,
14,
173-183)
copyright 2006.
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