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PDBsum entry 1jkt
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Contents |
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* Residue conservation analysis
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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 structures of the catalytic domain of human protein kinase associated with apoptosis and tumor suppression.
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Authors
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V.Tereshko,
M.Teplova,
J.Brunzelle,
D.M.Watterson,
M.Egli.
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Ref.
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Nat Struct Biol, 2001,
8,
899-907.
[DOI no: ]
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PubMed id
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Abstract
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We have determined X-ray crystal structures with up to 1.5 A resolution of the
catalytic domain of death-associated protein kinase (DAPK), the first described
member of a novel family of pro-apoptotic and tumor-suppressive serine/threonine
kinases. The geometry of the active site was studied in the apo form, in a
complex with nonhydrolyzable AMPPnP and in a ternary complex consisting of
kinase, AMPPnP and either Mg2+ or Mn2+. The structures revealed a previously
undescribed water-mediated stabilization of the interaction between the lysine
that is conserved in protein kinases and the beta- and gamma-phosphates of ATP,
as well as conformational changes at the active site upon ion binding.
Comparison between these structures and nucleotide triphosphate complexes of
several other kinases disclosed a number of unique features of the DAPK
catalytic domain, among which is a highly ordered basic loop in the N-terminal
domain that may participate in enzyme regulation.
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Figure 1.
Figure 1. Domain organization of DAPK (numbers refer to amino
acids).
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Figure 5.
Figure 5. Lattice interactions in the orthorhombic and cubic
crystal forms of the DAPK catalytic domain. a, Orthorhombic
form. Overview of the environment of the putative
peptide-binding region preceding the F-helix and the basic loop
linking  3
and helix C. Three symmetry mates colored blue, pink and cyan
make up the immediate surroundings of the loop region of each
DAPK molecule (red). Secondary structure elements are
represented as cylinders and arrows, and AMPPnP molecules and
four residues of the C-terminal streptavidin-tag visible in the
electron density maps are in a ball-and-stick representation. b,
Cubic form. The crystallographic asymmetric unit consists of
DAPK dimers related by a noncrystallographic two-fold rotation
axis running approximately along the vertical in the plane of
projection. Thus, basic loops and peptide binding regions of the
two molecules face each other.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2001,
8,
899-907)
copyright 2001.
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