5GLJ

Crystal Structure of PDZ1 Domain of Human Protein Tyrosine Phosphatase PTP-Bas

Summary for 5GLJ

• Entry DOI: 10.2210/pdb5glj/pdb
• Descriptor: Tyrosine-protein phosphatase non-receptor type 13, CHLORIDE ION (3 entities in total)
• Functional Keywords: ptp-bas, pdz1 domain, hydrolase
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm, cytoskeleton : Q12923
• Total number of polymer chains: 4
• Total formula weight: 40600.09

Authors

Lee, S.O.,Ku, B.,Chi, S.W. (deposition date: 2016-07-11, release date: 2016-11-23, Last modification date: 2024-03-20)

Primary citation

Lee, S.O.,Lee, M.K.,Ku, B.,Bae, K.H.,Lee, S.C.,Lim, H.M.,Kim, S.J.,Chi, S.W.
High-resolution crystal structure of the PDZ1 domain of human protein tyrosine phosphatase PTP-Bas.
Biochem.Biophys.Res.Commun., 478:1205-1210, 2016

PubMed Abstract: Protein tyrosine phosphatase-Basophil (PTP-Bas) is a membrane-associated protein tyrosine phosphatase with five PDZ domains and is involved in apoptosis, tumorigenesis, and insulin signaling. The interaction between PTP-Bas and tandem-PH-domain-containing protein 1/2 (TAPP1/2) plays an essential role in the regulation of insulin signaling. Despite its high sequence homology with the other PDZ domains, only the PDZ1 domain of PTP-Bas showed distinct binding specificity for TAPP1/2. Although the interaction between PTP-Bas PDZ1 and TAPP1/2 is a therapeutic target for diabetes, the structural basis for the interaction has not been elucidated. In the present study, we determined the crystal structure of the PTP-Bas PDZ1 domain at 1.6 Å resolution. In addition, we calculated the structural models of complexes of PTP-Bas PDZ1 and the C-terminal peptides of TAPP1/2 (referred to as TAPP1p/2p). Structural comparison with the PTP-Bas PDZ2/RA-GEF2 peptide complex revealed a structural basis for distinct binding specificity of PTP-Bas PDZ1 for TAPP1p/2p peptides. Our high-resolution crystal structure of PTP-Bas PDZ1 will serve as a useful template for rational structure-based design of novel anti-diabetes therapeutics.

PubMed: 27544031
DOI: 10.1016/j.bbrc.2016.08.095

Experimental method

X-RAY DIFFRACTION (1.6 Å)