Crystal Structure of the Catalytic Domain of Human RPTPH

Overview

Journal Acta Crystallogr F Struct Biol Commun

Specialty Chemistry

Date 2022 Jul 5

PMID 35787553

Authors

Myeongbin Kim

Seong Eon Ryu

Affiliations

Soon will be listed here.

Abstract

Receptor-type protein tyrosine phosphatases (RPTPs) receive extracellular stimuli and transfer them into cells. They regulate cell growth, differentiation and death via specific signals. They have also been implicated in cancer, diabetes and neurological diseases. RPTPH, a member of the type 3 RPTP (R3-PTP) family, is an important regulator of colorectal cancer and hepatic carcinoma. Despite its importance in drug development, the structure of RPTPH has not yet been resolved. Here, the crystal structure of the catalytic domain of RPTPH was determined at 1.56 Å resolution. Despite similarities to other R3-PTPs in its overall structure, RPTPH exhibited differences in its loop regions and side-chain conformations. Compared with other R3-PTPs, RPTPH has unique side chains near its active site that may confer specificity for inhibitor binding. Therefore, detailed information on the structure of RPTPH provides clues for the development of specific inhibitors.

Citing Articles

PTPRH promotes the progression of non-small cell lung cancer via glycolysis mediated by the PI3K/AKT/mTOR signaling pathway.

Wang S, Cheng Z, Cui Y, Xu S, Luan Q, Jing S J Transl Med. 2023; 21(1):819.

PMID: 37974250 PMC: 10652596. DOI: 10.1186/s12967-023-04703-5.

References

Mohebiany A, Nikolaienko R, Bouyain S, Harroch S . Receptor-type tyrosine phosphatase ligands: looking for the needle in the haystack. FEBS J. 2012; 280(2):388-400. PMC: 3753797. DOI: 10.1111/j.1742-4658.2012.08653.x. View

Zhang Y, Roos M, Himburg H, Termini C, Quarmyne M, Li M . PTPσ inhibitors promote hematopoietic stem cell regeneration. Nat Commun. 2019; 10(1):3667. PMC: 6694155. DOI: 10.1038/s41467-019-11490-5. View

Bunkoczi G, Read R . Improvement of molecular-replacement models with Sculptor. Acta Crystallogr D Biol Crystallogr. 2011; 67(Pt 4):303-12. PMC: 3069745. DOI: 10.1107/S0907444910051218. View

Tonks N . Protein tyrosine phosphatases: from genes, to function, to disease. Nat Rev Mol Cell Biol. 2006; 7(11):833-46. DOI: 10.1038/nrm2039. View

Sato T, Soejima K, Arai E, Hamamoto J, Yasuda H, Arai D . Prognostic implication of PTPRH hypomethylation in non-small cell lung cancer. Oncol Rep. 2015; 34(3):1137-45. PMC: 4530927. DOI: 10.3892/or.2015.4082. View

Barr A, Ugochukwu E, Lee W, King O, Filippakopoulos P, Alfano I . Large-scale structural analysis of the classical human protein tyrosine phosphatome. Cell. 2009; 136(2):352-63. PMC: 2638020. DOI: 10.1016/j.cell.2008.11.038. View

Otwinowski Z, Borek D, Majewski W, Minor W . Multiparametric scaling of diffraction intensities. Acta Crystallogr A. 2003; 59(Pt 3):228-34. DOI: 10.1107/s0108767303005488. View

Ito T, Okazawa H, Maruyama K, Tomizawa K, Motegi S, Ohnishi H . Interaction of SAP-1, a transmembrane-type protein-tyrosine phosphatase, with the tyrosine kinase Lck. Roles in regulation of T cell function. J Biol Chem. 2003; 278(37):34854-63. DOI: 10.1074/jbc.M300648200. View

Evdokimov A, Pokross M, Walter R, Mekel M, Cox B, Li C . Engineering the catalytic domain of human protein tyrosine phosphatase beta for structure-based drug discovery. Acta Crystallogr D Biol Crystallogr. 2006; 62(Pt 12):1435-45. DOI: 10.1107/S0907444906037784. View

10.

Seo Y, Matozaki T, Tsuda M, Hayashi Y, Itoh H, Kasuga M . Overexpression of SAP-1, a transmembrane-type protein tyrosine phosphatase, in human colorectal cancers. Biochem Biophys Res Commun. 1997; 231(3):705-11. DOI: 10.1006/bbrc.1997.6139. View

11.

McCoy A, Grosse-Kunstleve R, Adams P, Winn M, Storoni L, Read R . Phaser crystallographic software. J Appl Crystallogr. 2009; 40(Pt 4):658-674. PMC: 2483472. DOI: 10.1107/S0021889807021206. View

12.

Almo S, Bonanno J, Sauder J, Emtage S, DiLorenzo T, Malashkevich V . Structural genomics of protein phosphatases. J Struct Funct Genomics. 2007; 8(2-3):121-40. PMC: 4163028. DOI: 10.1007/s10969-007-9036-1. View

13.

Chen V, Arendall 3rd W, Headd J, Keedy D, Immormino R, Kapral G . MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr D Biol Crystallogr. 2010; 66(Pt 1):12-21. PMC: 2803126. DOI: 10.1107/S0907444909042073. View

14.

Yu K, Kim Y, Jung S, Ku B, Park H, Cho S . Structural basis for the dephosphorylating activity of PTPRQ towards phosphatidylinositide substrates. Acta Crystallogr D Biol Crystallogr. 2013; 69(Pt 8):1522-9. DOI: 10.1107/S0907444913010457. View

15.

Takada T, Noguchi T, Inagaki K, Hosooka T, Fukunaga K, Yamao T . Induction of apoptosis by stomach cancer-associated protein-tyrosine phosphatase-1. J Biol Chem. 2002; 277(37):34359-66. DOI: 10.1074/jbc.M206541200. View

16.

Jeffrey K, Camps M, Rommel C, Mackay C . Targeting dual-specificity phosphatases: manipulating MAP kinase signalling and immune responses. Nat Rev Drug Discov. 2007; 6(5):391-403. DOI: 10.1038/nrd2289. View

17.

Alonso A, Pulido R . The extended human PTPome: a growing tyrosine phosphatase family. FEBS J. 2015; 283(8):1404-29. DOI: 10.1111/febs.13600. View

18.

Emsley P, Lohkamp B, Scott W, Cowtan K . Features and development of Coot. Acta Crystallogr D Biol Crystallogr. 2010; 66(Pt 4):486-501. PMC: 2852313. DOI: 10.1107/S0907444910007493. View

19.

den Hertog J, Blanchetot C, Buist A, Overvoorde J, VAN DER SAR A, Tertoolen L . Receptor protein-tyrosine phosphatase signalling in development. Int J Dev Biol. 2000; 43(7):723-33. View

20.

Wiesmann C, Barr K, Kung J, Zhu J, Erlanson D, Shen W . Allosteric inhibition of protein tyrosine phosphatase 1B. Nat Struct Mol Biol. 2004; 11(8):730-7. DOI: 10.1038/nsmb803. View