PDBsum entry 3lny

Signaling protein/signaling protein

PDB id: 3lny

Contents

Protein chain

94 a.a. *

Ligands

GLU-GLN-VAL-SER-ALA-VAL

SCN

SO4 ×2

Waters ×238

* Residue conservation analysis

PDB id:

3lny

Name:

Signaling protein/signaling protein

Title:

Second pdz domain from human ptp1e in complex with ra-gef2 peptide

Structure:

Tyrosine-protein phosphatase non-receptor type 13. Chain: a. Fragment: pdz2 domain. Synonym: protein-tyrosine phosphatase 1e, ptp-e1, hptpe1, ptp-bas, protein-tyrosine phosphatase ptpl1, fas-associated protein-tyrosine phosphatase 1, fap-1. Engineered: yes. Rap guanine nucleotide exchange factor 6. Chain: b.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ptpn13, pnp1, ptp1e, ptpl1. Expressed in: escherichia coli. Expression_system_taxid: 469008. Gene: rapgef6, pdzgef2

Resolution:

1.30Å R-factor: 0.164 R-free: 0.189

Authors:

J.Zhang,A.Chang,H.Ke,G.N.Phillips Jr.,A.L.Lee,Center For Eukaryotic Structural Genomics (Cesg)

Key ref:

J.Zhang et al. (2010). Crystallographic and nuclear magnetic resonance evaluation of the impact of peptide binding to the second PDZ domain of protein tyrosine phosphatase 1E. Biochemistry, 49, 9280-9291. PubMed id: 20839809

Date:

03-Feb-10 Release date: 23-Mar-10

Protein chain

Q12923  (PTN13_HUMAN) -  Tyrosine-protein phosphatase non-receptor type 13 from Homo sapiens

Seq: 2485 a.a.

Struc: 94 a.a.

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

Biochemistry 49:9280-9291 (2010)

PubMed id: 20839809

Crystallographic and nuclear magnetic resonance evaluation of the impact of peptide binding to the second PDZ domain of protein tyrosine phosphatase 1E.

J.Zhang, P.J.Sapienza, H.Ke, A.Chang, S.R.Hengel, H.Wang, G.N.Phillips, A.L.Lee.

ABSTRACT

PDZ (PSD95/Discs large/ZO-1) domains are ubiquitous protein interaction motifs found in scaffolding proteins involved in signal transduction. Despite the fact that many PDZ domains show a limited tendency to undergo structural change, the PDZ family has been associated with long-range communication and allostery. One of the PDZ domains studied most in terms of structure and biophysical properties is the second PDZ ("PDZ2") domain from protein tyrosine phosphatase 1E (PTP1E, also known as PTPL1). Previously, we showed through NMR relaxation studies that binding of the RA-GEF2 C-terminal peptide substrate results in long-range propagation of side-chain dynamic changes in human PDZ2 [Fuentes, E. J., et al. (2004) J. Mol. Biol. 335, 1105-1115]. Here, we present the first X-ray crystal structures of PDZ2 in the absence and presence of RA-GEF2 ligand, determined to resolutions of 1.65 and 1.3 Å, respectively. These structures deviate somewhat from previously determined NMR structures and indicate that very minor structural changes in PDZ2 accompany peptide binding. NMR residual dipolar couplings confirm the crystal structures to be accurate models of the time-averaged atomic coordinates of PDZ2. The impact on side-chain dynamics was further tested with a C-terminal peptide from APC, which showed results nearly identical to those of RA-GEF2. Thus, allosteric transmission in PDZ2 induced by peptide binding is conveyed purely and robustly by dynamics. (15)N relaxation dispersion measurements did not detect appreciable populations of a kinetic structural intermediate. Collectively, for ligand binding to PDZ2, these data support a lock-and-key binding model from a structural perspective and an allosteric model from a dynamical perspective, which together suggest a complex energy landscape for functional transitions within the ensemble.