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PDBsum entry 1jm6
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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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Structure of pyruvate dehydrogenase kinase. Novel folding pattern for a serine protein kinase.
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Authors
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C.N.Steussy,
K.M.Popov,
M.M.Bowker-Kinley,
R.B.Sloan,
R.A.Harris,
J.A.Hamilton.
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Ref.
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J Biol Chem, 2001,
276,
37443-37450.
[DOI no: ]
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PubMed id
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Abstract
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The structure of mitochondrial pyruvate dehydrogenase kinase isozyme 2 is of
interest because it represents a family of serine-specific protein kinases that
lack sequence similarity with all other eukaryotic protein kinases. Similarity
exists instead with key motifs of prokaryotic histidine protein kinases and a
family of eukaryotic ATPases. The 2.5-A crystal structure reported here reveals
that pyruvate dehydrogenase kinase isozyme 2 has two domains of about the same
size. The N-terminal half is dominated by a bundle of four amphipathic
alpha-helices, whereas the C-terminal half is folded into an alpha/beta sandwich
that contains the nucleotide-binding site. Analysis of the structure reveals
this C-terminal domain to be very similar to the nucleotide-binding domain of
bacterial histidine kinases, but the catalytic mechanism appears similar to that
of the eukaryotic serine kinases and ATPases.
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Figure 2.
Fig. 2. Alignment of the PDK2 nucleotide-binding domain
with prokaryotic histidine kinases and ATPases. This figure
shows a composite of the C  tracings of
the ATP-binding domains of the structurally homologous ATPases
Hsp90 (Protein Data Bank (36) code 1AM1) residues 26-209, MutL
(1B62) residues 22-201, and DNA Gyrase B (1EI1) residues
452-619, as well as the histidine kinase CheA (1B3Q) residues
354-538, all of which were aligned with the C-terminal domain of
PDK2, residues 183-353, using the program TOP3D (17). The
backbone for all structures is shown in gray, and the nucleotide
is shown in color. Visualization was done with Swiss-PdbViewer
(38), and rendering was done with POV-Ray for Windows.
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Figure 5.
Fig. 5. Electrostatic surface of PDK2 compared with the
lipoyl domain. This figure shows a surface map of the PDK2
monomer and a modeled lipoyl domain. The colors are based on
charge density: red, negative charge; blue, positive charge;
white, neutral or hydrophobic. Both surface models were
generated in Swiss-PdbViewer (38) by mapping the
Poisson-Boltzmann electrostatic potential of the protein to
colors on the accessible molecular surface. Rendering was done
with POV-Ray for Windows (Cason, C., www.povray.org). A model of
a lipoyl domain was produced from the NMR structure of the L2
domain of human PDC (1FYC) with the rat L2 sequence (90%
identical to human) threaded on and energy minimized (38) The
colors are defined as for the PDK2 surface. The PDK2 monomer is
rotated away from the dimer interface to show the cleft between
the N- and C-terminal domains that is compatible in shape and
size to the lipoyl domain.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2001,
276,
37443-37450)
copyright 2001.
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