7f5o › Citations

Crystal Structure of TCPTP Unravels an Allosteric Regulatory Role of Helix α7 in Phosphatase Activity.

Singh JP, Lin MJ, Hsu SF, Peti W, Lee CC, Meng TC
Biochemistry 60 3856-3867 (2021)
Cited: 10 times
EuropePMC logo PMID: 34910875

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.

Articles - 7f5o mentioned but not cited (1)

  1. Discovery of a selective TC-PTP degrader for cancer immunotherapy. Miao J, Dong J, Miao Y, Bai Y, Qu Z, Jassim BA, Huang B, Nguyen Q, Ma Y, Murray AA, Li J, Low PS, Zhang ZY. Chem Sci 14 12606-12614 (2023)


Reviews citing this publication (2)

  1. Protein tyrosine phosphatase non-receptor type 2 as the therapeutic target of atherosclerotic diseases: past, present and future. Tang XE, Cheng YQ, Tang CK. Front Pharmacol 14 1219690 (2023)
  2. Recent applications of computational methods to allosteric drug discovery. Govindaraj RG, Thangapandian S, Schauperl M, Denny RA, Diller DJ. Front Mol Biosci 9 1070328 (2022)

Articles citing this publication (7)

  1. Conserved conformational dynamics determine enzyme activity. Torgeson KR, Clarkson MW, Granata D, Lindorff-Larsen K, Page R, Peti W. Sci Adv 8 eabo5546 (2022)
  2. Allosteric Inhibition of PTP1B by a Nonpolar Terpenoid. Friedman AJ, Liechty ET, Kramer L, Sarkar A, Fox JM, Shirts MR. J Phys Chem B 126 8427-8438 (2022)
  3. Room-temperature serial synchrotron crystallography of the human phosphatase PTP1B. Sharma S, Ebrahim A, Keedy DA. Acta Crystallogr F Struct Biol Commun 79 23-30 (2023)
  4. Analysis of neutral mutational drift in an allosteric enzyme. Liechty ET, Hren A, Kramer L, Donovan G, Friedman AJ, Shirts MR, Fox JM. Protein Sci 32 e4719 (2023)
  5. Evidence of Insulin-Sensitizing and Mimetic Activity of the Sesquiterpene Quinone Avarone, a Protein Tyrosine Phosphatase 1B and Aldose Reductase Dual Targeting Agent from the Marine Sponge Dysidea avara. Casertano M, Genovese M, Santi A, Pranzini E, Balestri F, Piazza L, Del Corso A, Avunduk S, Imperatore C, Menna M, Paoli P. Pharmaceutics 15 528 (2023)
  6. Biophysical Rationale for the Selective Inhibition of PTP1B over TCPTP by Nonpolar Terpenoids. Friedman AJ, Padgette HM, Kramer L, Liechty ET, Donovan GW, Fox JM, Shirts MR. J Phys Chem B 127 8305-8316 (2023)
  7. Macromolecular crowding amplifies allosteric regulation of T-cell protein tyrosine phosphatase. Tun MT, Yang S, Forti FL, Santelli E, Bottini N. J Biol Chem 298 102655 (2022)


Quick links