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PDBsum entry 2b3r
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the c2 domain of class ii phosphatidylinositide 3-Kinase c2{alpha}.
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Authors
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L.Liu,
X.Song,
D.He,
C.Komma,
A.Kita,
J.V.Virbasius,
G.Huang,
H.D.Bellamy,
K.Miki,
M.P.Czech,
G.W.Zhou.
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Ref.
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J Biol Chem, 2006,
281,
4254-4260.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
88%.
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Abstract
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Phosphatidylinositide (PtdIns) 3-kinase catalyzes the addition of a phosphate
group to the 3'-position of phosphatidyl inositol. Accumulated evidence shows
that PtdIns 3-kinase can provide a critical signal for cell proliferation, cell
survival, membrane trafficking, glucose transport, and membrane ruffling.
Mammalian PtdIns 3-kinases are divided into three classes based on structure and
substrate specificity. A unique characteristic of class II PtdIns 3-kinases is
the presence of both a phox homolog domain and a C2 domain at the C terminus.
The biological function of the C2 domain of the class II PtdIns 3-kinases
remains to be determined. We have determined the crystal structure of the
mCPK-C2 domain, which is the first three-dimensional structural model of a C2
domain of class II PtdIns 3-kinases. Structural studies reveal that the mCPK-C2
domain has a typical anti-parallel beta-sandwich fold. Scrutiny of the surface
of this C2 domain has identified three small, shallow sulfate-binding sites. On
the basis of the structural features of these sulfate-binding sites, we have
studied the lipid binding properties of the mCPK-C2 domain by site-directed
mutagenesis. Our results show that this C2 domain binds specifically to
PtdIns(3,4)P(2) and PtdIns(4,5)P(2) and that three lysine residues at SBS I
site, Lys-1420, Lys-1432, and Lys-1434, are responsible for the phospholipid
binding affinity.
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Figure 2.
Sulfate-binding sites of the mCPK-C2 domain. The 2 F[o] -
F[c] maps contoured at the 1σ level are shown in purple for SBS
I (A), SBS II (B), and SBS III (C), respectively. The sulfate
groups are shown in bond representation, with oxygen atoms
colored in red and sulfate atoms colored yellow. The surrounding
water molecules are shown as green spheres. Other residues in
the mCPK-C2 domain are depicted as bonds. Residues bound with
sulfate ions are labeled, and the interactions are shown as
dashed lines. D and E, the electrostatic potential surfaces of
the mCPK-C2 domain with the bound sulfate ions are shown.
Negatively charged regions are shown in red and positively
charged regions in blue. The sulfate ions shown in CPK model
with the same color coding as in panel A are labeled with the
corresponding sulfate-binding sites. SBSs I and III (D) and SBSs
I and II (E) are shown. CONSCRIPT (38) and GRASP (39) were used
to generate panels A-C and panels D and E, respectively.
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Figure 4.
Comparison of the mCPK-C2 domain with other type-I folded C2
domains. A, the Cα atoms of the mCPK-C2 domain in the
β-sandwich core region are superposed with the Cα atoms of
other type-I folded C2 domains and the C2 domains of Synaptagmin
I (1RSY), Synaptagmin III (1DQV), PKCα (1DSY), and PKCβ (1A25)
Their Cα chains are shown in red, purple, green, blue, and
cyan, respectively. Their bound ligands and/or ions are shown in
the same color as the Cα chains. For the structure of the
mCPK-C2 domain, every tenth residue and each β-strand are
labeled. In addition, the backbone of mCPK-C2 domain is rendered
as thick sticks, and the three bound sulfate ions are rendered
as ball-and-stick models with the same color coding as in Fig.
1A. B-D, comparison of the SBS I site in the mCPK-C2 domain (B)
with the corresponding ligand-binding site in the PCKβ-C2
domain (C) and the PCKα-C2 domain (D). The backbones are shown
in the same color as in panel A. The side chains of the residues
involved in ligand binding and the bound ligand in the complex
structure (sulfate, PS, and phosphate molecule in panels B, C,
and D, respectively) are shown with a ball-and-stick model, in
which red, blue, gray, and yellow represent the oxygen,
nitrogen, carbon, and sulfur/phosphorus atoms, respectively. The
bonds are colored in green for the protein and orange for the
bound ligands.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2006,
281,
4254-4260)
copyright 2006.
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