PDBsum entry 1vj6

Hydrolase/signaling protein

PDB id: 1vj6

Contents

Protein chain

95 a.a. *

Ligands

TYR-LEU-VAL-THR-SER-VAL

* Residue conservation analysis

PDB id:

1vj6

Name:

Hydrolase/signaling protein

Title:

Pdz2 from ptp-bl in complex with thE C-terminal ligand from the apc protein

Structure:

Protein-tyrosine-phosphatase (nonreceptor type 13). Chain: a. Fragment: pdz2 domain. Engineered: yes. Adenomatous polyposis coli protein. Chain: b. Fragment: c-terminus of apc. Synonym: apc protein, mapc. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: ptp-bl. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: this protein has been chemically synthesized. It is present in mouse.

NMR struc:

35 models

Authors:

T.Walma,G.W.Vuister

Key ref:

S.Gianni et al. (2006). Demonstration of long-range interactions in a PDZ domain by NMR, kinetics, and protein engineering. Structure, 14, 1801-1809. PubMed id: 17161370 DOI: 10.1016/j.str.2006.10.010

Date:

03-Feb-04 Release date: 01-Nov-05

Protein chain

Q64512  (PTN13_MOUSE) -  Tyrosine-protein phosphatase non-receptor type 13 from Mus musculus

Seq: 2453 a.a.

Struc: 95 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.1.3.48 - protein-tyrosine-phosphatase.
• Reaction: O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate

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

Key reference

DOI no: 10.1016/j.str.2006.10.010

Structure 14:1801-1809 (2006)

PubMed id: 17161370

Demonstration of long-range interactions in a PDZ domain by NMR, kinetics, and protein engineering.

S.Gianni, T.Walma, A.Arcovito, N.Calosci, A.Bellelli, A.Engström, C.Travaglini-Allocatelli, M.Brunori, P.Jemth, G.W.Vuister.

ABSTRACT

Understanding the basis of communication within protein domains is a major challenge in structural biology. We present structural and dynamical evidence for allosteric effects in a PDZ domain, PDZ2 from the tyrosine phosphatase PTP-BL, upon binding to a target peptide. The NMR structures of its free and peptide-bound states differ in the orientation of helix alpha2 with respect to the remainder of the molecule, concomitant with a readjustment of the hydrophobic core. Using an ultrafast mixing instrument, we detected a deviation from simple bimolecular kinetics for the association with peptide that is consistent with a rate-limiting conformational change in the protein (k(obs) approximately 7 x 10(3) s(-1)) and an induced-fit model. Furthermore, the binding kinetics of 15 mutants revealed that binding is regulated by long-range interactions, which can be correlated with the structural rearrangements resulting from peptide binding. The homologous protein PSD-95 PDZ3 did not display a similar ligand-induced conformational change.

Selected figure(s)

Figure 1.
Figure 1. Structures of PDZ Domains
(A) Overlay of the ensemble of 35 NMR-derived structures of the PDZ2-peptide complex colored as a rainbow ramp ranging from blue (N terminus) to red (C terminus). The peptide is shown in stick representation. For clarity, only the last five C-terminal residues of the peptide are displayed.
(B) Superposition of the structures of PDZ2 in the free (green, helix α2 in pink, PDB code 1GM1) and complexed (blue, helix α2 in cyan, peptide in red) states.
(C) Superposition between the structures of PDZ3 in the free and complexed states (PDB codes 1BFE and 1BE9, respectively). Color coding as in (B).

Figure 4.
Figure 4. Peptide Binding to Mutant PDZ Domains
Stopped-flow data on representative mutants of PDZ domains. Mutants were classified into three categories: those primarily altering the association rate constant (A), the dissociation rate constant (B), or both (C). See Table 2 for rate constants. (D) Effect of mutagenesis on binding. PDZ2 is shown in ribbon representation (gray); residues affected by mutagenesis in space-filling representation. Blue-colored residues primarily alter the association rate constant, salmon-colored residues affect the dissociation rate constant, whereas magenta-colored residues affect both rate constants. The P[−3]-P[0] residues of the APC-peptide are also shown in red by using stick representation.

The above figures are reprinted by permission from Cell Press: Structure (2006, 14, 1801-1809) copyright 2006.

Figures were selected by an automated process.