2B3O

Crystal structure of human tyrosine phosphatase SHP-1

Summary for 2B3O

• Entry DOI: 10.2210/pdb2b3o/pdb
• Related: 1FPR 1GWZ
• Descriptor: Tyrosine-protein phosphatase, non-receptor type 6 (2 entities in total)
• Functional Keywords: protein tyrosine phosphatase, shp-1, signaling, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P29350
• Total number of polymer chains: 1
• Total formula weight: 60350.73

Authors

Yang, J.,Liu, L.,He, D.,Song, X.,Liang, X.,Zhao, Z.J.,Zhou, G.W. (deposition date: 2005-09-20, release date: 2005-10-25, Last modification date: 2024-02-14)

Primary citation

Yang, J.,Liu, L.,He, D.,Song, X.,Liang, X.,Zhao, Z.J.,Zhou, G.W.
Crystal structure of human protein-tyrosine phosphatase SHP-1.
J.Biol.Chem., 278:6516-6520, 2003

PubMed Abstract: SHP-1 is a cytosolic protein-tyrosine phosphatase that behaves as a negative regulator in eukaryotic cellular signaling pathways. To understand its regulatory mechanism, we have determined the crystal structure of the C-terminal truncated human SHP-1 in the inactive conformation at 2.8-A resolution and refined the structure to a crystallographic R-factor of 24.0%. The three-dimensional structure shows that the ligand-free SHP-1 has an auto-inhibited conformation. Its N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, which supports that the phosphatase activity of SHP-1 is primarily regulated by the N-SH2 domain. In addition, the C-SH2 domain of SHP-1 has a different orientation from and is more flexible than that of SHP-2, which enables us to propose an enzymatic activation mechanism in which the C-SH2 domains of SHPs could be involved in searching for phosphotyrosine activators.

PubMed: 12482860
DOI: 10.1074/jbc.M210430200

Experimental method

X-RAY DIFFRACTION (2.8 Å)