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PDBsum entry 1qz2
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Isomerase/chaperone
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PDB id
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1qz2
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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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3d structure of human fk506-Binding protein 52: implications for the assembly of the glucocorticoid receptor/hsp90/immunophilin heterocomplex.
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Authors
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B.Wu,
P.Li,
Y.Liu,
Z.Lou,
Y.Ding,
C.Shu,
S.Ye,
M.Bartlam,
B.Shen,
Z.Rao.
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Ref.
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Proc Natl Acad Sci U S A, 2004,
101,
8348-8353.
[DOI no: ]
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PubMed id
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Abstract
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FK506-binding protein 52 (FKBP52), which binds FK506 and possesses
peptidylprolyl isomerase activity, is an important immunophilin involved in the
heterocomplex of steroid receptors with heat-shock protein 90. Here we report
of
FKBP52 and the complex with a C-terminal pentapeptide from heat-shock protein
90. Based on the structures of these two overlapped fragments, the complete
putative structure of FKBP52 can be defined. The structure of FKBP52 is composed
of two consecutive FKBP domains, a tetratricopeptide repeat domain and a short
helical domain beyond the final tetratricopeptide repeat motif. Key structural
differences between FKBP52 and FKBP51, including the relative orientations of
the four domains and some important residue substitutions, could account for the
differential functions of FKBPs.
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Figure 2.
Fig. 2. Stereo view of the superposition of FK and TPR
domains. (a) Two FKBP domains of FKBP51 and FKBP52 were
superimposed onto FKBP12. FKBP12 (green), 51-FK1 (blue), and
52-FK1 (red) are similar. The structures of 51-FK2 (cyan) and
52-FK2 (yellow) are more closed than the others. (b) TPR domains
are superimposed onto the TPR domains of FKBP52. FKBP52 is shown
in yellow, FKBP51 is shown in cyan, Hop is shown in green, Cyp40
is shown in purple, and PP5 is shown in pink. The conformations
of all the TPR domains are similar, containing six  -helices
( 1- 6). The orientations of
the extra -helix ( 7) are
different. (c) Superposition of the structures of TPR domains
and the 7-helixes of FKBP51
(blue) and FKBP52 (yellow). Gln-333, Phe-335, and Ala-365 of
FKBP52 are replaced by Arg-331, Tyr-333, and Leu-363 in FKBP51,
which may be responsible for the differential binding pattern of
FKBPs to Hsp90. The side chain of Ile-400 of FKBP52,
corresponding to Ala-398 of FKBP51, will clash with Phe-369, and
this may cause the different orientations of the 7-helix.
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Figure 3.
Fig. 3. (a) Stereo view of the hydrogen bonds between FK1
and FK2 of FKBP52. Hydrogen bonds at the interface of FK1 and
FK2 form a complicated network, which stabilizes the
conformation. Residues in FK1 are shown in red, residues in FK2
are shown in yellow, and residues in the loop are shown in
white. (b and c) Stereo view of the MEEVD peptide bound to
molecules A (b)and B(c) of C(145-459). The omit electron-density
map is contoured at 0.7  above the mean.
Residues of the peptide are shown in white, and residues of the
TPR domain are shown in yellow. Residues involved in important
interactions are shown in ball-and-stick representation.
Hydrogen bonds are shown as dotted lines.
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