PDBsum entry 1i6c

Isomerase

PDB id: 1i6c

Contents

Protein chain

39 a.a. *

* Residue conservation analysis

PDB id:

1i6c

Name:

Isomerase

Title:

Solution structure of pin1 ww domain

Structure:

Peptidyl-prolyl cis-trans isomerase nima-interacting 1. Chain: a. Fragment: ww domain (residues 6-44). Engineered: yes

Source:

Synthetic: yes. Other_details: the pin1 ww domain was obtained by peptide synthesis using the boc-benzyl strategy and the hbtu in situ activation protocol on a applied biosystems 430a peptide synthesizer. The protein is naturally found in homo sapiens (human).

NMR struc:

10 models

Authors:

R.Wintjens,J.-M.Wieruszeski,H.Drobecq,G.Lippens,I.Landrieu

Key ref:

R.Wintjens et al. (2001). 1H NMR study on the binding of Pin1 Trp-Trp domain with phosphothreonine peptides. J Biol Chem, 276, 25150-25156. PubMed id: 11313338 DOI: 10.1074/jbc.M010327200

Date:

02-Mar-01 Release date: 18-Jul-01

Protein chain

Q13526  (PIN1_HUMAN) -  Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 from Homo sapiens

Seq: 163 a.a.

Struc: 39 a.a.

Enzyme reactions

• Enzyme class: E.C.5.2.1.8 - peptidylprolyl isomerase.
• Reaction: [protein]-peptidylproline (omega=180) = [protein]-peptidylproline (omega=0)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1074/jbc.M010327200

J Biol Chem 276:25150-25156 (2001)

PubMed id: 11313338

1H NMR study on the binding of Pin1 Trp-Trp domain with phosphothreonine peptides.

R.Wintjens, J.M.Wieruszeski, H.Drobecq, P.Rousselot-Pailley, L.Buée, G.Lippens, I.Landrieu.

ABSTRACT

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.

Selected figure(s)

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.

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.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2001, 276, 25150-25156) copyright 2001.

Figures were selected by an automated process.