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PDBsum entry 2k5b
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References listed in PDB file
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Key reference
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Title
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The human cdc37.Hsp90 complex studied by heteronuclear nmr spectroscopy.
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Authors
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S.Sreeramulu,
H.R.Jonker,
T.Langer,
C.Richter,
C.R.Lancaster,
H.Schwalbe.
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Ref.
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J Biol Chem, 2009,
284,
3885-3896.
[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 have
been manually determined.
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Abstract
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The cell division cycle protein 37 (Cdc37) and the 90-kDa heat shock protein
(Hsp90) are molecular chaperones, which are crucial elements in the protein
signaling pathway. The largest class of client proteins for Cdc37 and Hsp90 are
protein kinases. The catalytic domains of these kinases are stabilized by Cdc37,
and their proper folding and functioning is dependent on Hsp90. Here, we present
the x-ray crystal structure of the 16-kDa middle domain of human Cdc37 at 1.88
angstroms resolution and the structure of this domain in complex with the 23-kDa
N-terminal domain of human Hsp90 based on heteronuclear solution state NMR data
and docking. Our results demonstrate that the middle domain of Cdc37 exists as a
monomer. NMR and mutagenesis experiments reveal Leu-205 in Cdc37 as a key
residue enabling complex formation. These findings can be very useful in the
development of small molecule inhibitors against cancer.
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Figure 6.
Schematic representation of the interaction interface of NMR
calculated Cdc37[M]·Hsp90[N] complex structure. The
positively charged, negatively charged, neutral, and hydrophobic
amino acids are colored in red, blue, green, and gray,
respectively.
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Figure 8.
Sequence alignment of human Hsp90[N] and yeast Hsp90[N]. The
shaded region is the region that interacts with Cdc37[M] and
forms the hydrophobic core of the interface.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2009,
284,
3885-3896)
copyright 2009.
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