PDBsum entry 1nmv

Isomerase

PDB id: 1nmv

Contents

Protein chain

163 a.a. *

* Residue conservation analysis

PDB id:

1nmv

Name:

Isomerase

Title:

Solution structure of human pin1

Structure:

Peptidyl-prolyl cis-trans isomerase nima-interacting 1. Chain: a. Synonym: rotamase pin1, ppiase pin1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: pin1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

NMR struc:

10 models

Authors:

E.Bayer,S.Goettsch,J.W.Mueller,B.Griewel,E.Guiberman,L.Mayr,P.Bayer

Key ref:

E.Bayer et al. (2003). Structural analysis of the mitotic regulator hPin1 in solution: insights into domain architecture and substrate binding. J Biol Chem, 278, 26183-26193. PubMed id: 12721297 DOI: 10.1074/jbc.M300721200

Date:

11-Jan-03 Release date: 12-Aug-03

Protein chain

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

Seq: 163 a.a.

Struc: 163 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.M300721200

J Biol Chem 278:26183-26193 (2003)

PubMed id: 12721297

Structural analysis of the mitotic regulator hPin1 in solution: insights into domain architecture and substrate binding.

E.Bayer, S.Goettsch, J.W.Mueller, B.Griewel, E.Guiberman, L.M.Mayr, P.Bayer.

ABSTRACT

The peptidyl-prolyl cis/trans isomerase hPin1 is a phosphorylation-dependent regulatory enzyme whose substrates are proteins involved in regulation of cell cycle, transcription, Alzheimer's disease, and cancer pathogenesis. We have determined the solution structure of the two domain protein hPin1-(1-163) and its separately expressed PPIase domain (50-163) (hPin1PPIase) with an root mean square deviation of <0.5 A over backbone atoms using NMR. Domain organization of hPin1 differs from that observed in structures solved by x-ray crystallography. Whereas PPIase and WW domain are tightly packed onto each other and share a common binding interface in crystals, our NMR-based data revealed only weak interaction of both domains at their interface in solution. Interaction between the two domains of full-length hPin1 is absent when the protein is dissected into the catalytic and the WW domain. It indicates that the flexible linker, connecting both domains, promotes binding. By evaluation of NOESY spectra we can show that the alpha1/beta1 loop, which was proposed to undergo a large conformational rearrangement in the absence of sulfate and an Ala-Pro peptide, remained in the closed conformation under these conditions. Dissociation constants of 0.4 and 2.0 mm for sulfate and phosphate ions were measured at 12 degrees C by fluorescence spectroscopy. Binding of sulfate prevents hPin1 aggregation and changes surface charges across the active center and around the reactive and catalytically essential Cys113. In the absence of sulfate and/or reducing agent this residue seems to promote aggregation, as observed in hPin1 solutions in vitro.

Selected figure(s)

Figure 4.
FIG. 4. Structural comparison of solution and crystal structures of the PPIase domain of hPin1. Top, the C[ ]trace of the PPIase domain of the solution structure (red) is superimposed with the crystal structure solved by Verdecia et al. (13) (blue) (A) and Ranganathan et al. (14) (cyan) (B). Bottom, differences in angles between the solution structure and crystal structures from A and B are plotted.

Figure 9.
FIG. 9. GRASP surface representation of hPin1[PPIase]. Molecular surfaces are colored according to electric potential. Blue colors represent positive charges, red colors are negative charges, and neutral areas are gray. Calculation of electric potential was done, including the potential of the complexed sulfate ion (A) or excluding it (B). Indicated are charged residues and amino acids of the active center.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 26183-26193) copyright 2003.

Figures were selected by an automated process.