7F5O

Crystal structure of PTPN2 catalytic domain

Summary for 7F5O

• Entry DOI: 10.2210/pdb7f5o/pdb
• Descriptor: Tyrosine-protein phosphatase non-receptor type 2, IODIDE ION (3 entities in total)
• Functional Keywords: protein tyrosine phosphatase, tcptp, ptpn2, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 3
• Total formula weight: 107213.98

Authors

Singh, J.P.,Lin, M.-J.,Hsu, S.-F.,Lee, C.-C.,Meng, T.-C. (deposition date: 2021-06-22, release date: 2021-12-29, Last modification date: 2023-11-29)

Primary citation

Singh, J.P.,Lin, M.J.,Hsu, S.F.,Peti, W.,Lee, C.C.,Meng, T.C.
Crystal Structure of TCPTP Unravels an Allosteric Regulatory Role of Helix alpha 7 in Phosphatase Activity.
Biochemistry, 60:3856-3867, 2021

PubMed Abstract: The T-cell protein tyrosine phosphatase (TCPTP/PTPN2) targets a broad variety of substrates across different subcellular compartments. In spite of that, the structural basis for the regulation of TCPTP's activity remains elusive. Here, we investigated whether the activity of TCPTP is regulated by a potential allosteric site in a comparable manner to its most similar PTP family member (PTP1B/PTPN1). We determined two crystal structures of TCPTP at 1.7 and 1.9 Å resolutions that include helix α7 at the TCPTP C-terminus. Helix α7 has been functionally characterized in PTP1B and was identified as its allosteric switch. However, its function is unknown in TCPTP. Here, we demonstrate that truncation or deletion of helix α7 reduced the catalytic efficiency of TCPTP by ∼4-fold. Collectively, our data supports an allosteric role of helix α7 in regulation of TCPTP's activity, similar to its function in PTP1B, and highlights that the coordination of helix α7 with the core catalytic domain is essential for the efficient catalytic function of TCPTP.

PubMed: 34910875
DOI: 10.1021/acs.biochem.1c00519

Experimental method

X-RAY DIFFRACTION (1.7 Å)