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PDBsum entry 1i8g
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Hydrolase/isomerase
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PDB id
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1i8g
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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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1h nmr study on the binding of pin1 trp-Trp domain with phosphothreonine peptides.
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Authors
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R.Wintjens,
J.M.Wieruszeski,
H.Drobecq,
P.Rousselot-Pailley,
L.Buée,
G.Lippens,
I.Landrieu.
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Ref.
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J Biol Chem, 2001,
276,
25150-25156.
[DOI no: ]
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PubMed id
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Abstract
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The recent crystal structure of Pin1 protein bound to a doubly phosphorylated
peptide from the C-terminal domain of RNA polymerase II revealed that binding
interactions between Pin1 and its substrate take place through its Trp-Trp (WW)
domain at the level of the loop Ser(11)-Arg(12) and the aromatic pair
Tyr(18)-Trp(29), and showed a trans conformation for both pSer-Pro peptide
bonds. However, the orientation of the ligand in the aromatic recognition groove
still could be sequence-specific, as previously observed in SH3 domains
complexed by peptide ligands or for different class of WW domains (Zarrinpar,
A., and Lim, W. A. (2000) Nat. Struct. Biol. 7, 611-613). Because the bound
peptide conformation could also differ as observed for peptide ligands bound to
the 14-3-3 domain, ligand orientation and conformation for two other
biologically relevant monophosphate substrates, one derived from the Cdc25
phosphatase of Xenopus laevis (EQPLpTPVTDL) and another from the human tau
protein (KVSVVRpTPPKSPS) in complex with the WW domain are here studied by
solution NMR methods. First, the proton resonance perturbations on the WW domain
upon complexation with both peptide ligands were determined to be essentially
located in the positively charged beta-hairpin Ser(11)-Gly(15) and around the
aromatic Trp(29). Dissociation equilibrium constants of 117 and 230 microm for
Cdc25 and tau peptides, respectively, were found. Several intermolecular nuclear
Overhauser effects between WW domain and substrates were obtained from a
ligand-saturated solution and were used to determine the structures of the
complexes in solution. We found a similar N to C orientation as the one observed
in the crystal complex structure of Pin1 and a trans conformation for the
pThr-Pro peptidic bond in both peptide ligands, thereby indicating a unique
binding scheme for the Pin1 WW domain to its multiple substrates.
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Figure 5.
Fig. 5. Stereo view of the overlaid backbone traces of
the 20 final conformers of the complex between the Pin1 WW
domain and a Cdc25 peptide ligand. Superposition was done on
residues (4-32) of the WW domain.
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Figure 6.
Fig. 6. Ribbon drawing of the NMR reference structure of
the complex between Pin1 WW domain (in light blue) and 
phosphopeptide ligand (in red), in comparison with the
orientation of the CTD peptide (in violet) from the
crystallographic model of the complex (13). The image was
obtained by backbone superimposition of WW domains from our NMR
complex and from the CTD peptide/Pin1 complex (13). Only the WW
domain from this study and both phosphopeptide ligands are
represented. Side chains implicated into the binding interface
are labeled (in white for the WW domain residues and yellow for
the ligand residues) and depicted in detail, as well as the
amino acid pair Trp6-Pro32 of the WW domain. N atoms are blue
and P atoms are violet. C atoms are green in the WW domain and
orange in the tau ligand.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2001,
276,
25150-25156)
copyright 2001.
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