» Articles » PMID: 26057789

Structure of Human Dual-specificity Phosphatase 7, a Potential Cancer Drug Target

Overview
Specialty Chemistry
Date 2015 Jun 10
PMID 26057789
Citations 3
Authors
Affiliations
Soon will be listed here.
Abstract

Human dual-specificity phosphatase 7 (DUSP7/Pyst2) is a 320-residue protein that belongs to the mitogen-activated protein kinase phosphatase (MKP) subfamily of dual-specificity phosphatases. Although its precise biological function is still not fully understood, previous reports have demonstrated that DUSP7 is overexpressed in myeloid leukemia and other malignancies. Therefore, there is interest in developing DUSP7 inhibitors as potential therapeutic agents, especially for cancer. Here, the purification, crystallization and structure determination of the catalytic domain of DUSP7 (Ser141-Ser289/C232S) at 1.67 Å resolution are reported. The structure described here provides a starting point for structure-assisted inhibitor-design efforts and adds to the growing knowledge base of three-dimensional structures of the dual-specificity phosphatase family.

Citing Articles

In Vitro and In Silico Investigation of BCI Anticancer Properties and Its Potential for Chemotherapy-Combined Treatments.

Marciniak B, Kciuk M, Mujwar S, Sundaraj R, Bukowski K, Gruszka R Cancers (Basel). 2023; 15(18).

PMID: 37760412 PMC: 10526149. DOI: 10.3390/cancers15184442.


Mitogen-Activated Protein Kinase Phosphatases: No Longer Undruggable?.

Shillingford S, Bennett A Annu Rev Pharmacol Toxicol. 2023; 63:617-636.

PMID: 36662585 PMC: 10127142. DOI: 10.1146/annurev-pharmtox-051921-121923.


Dual specificity phosphatase 7 drives the formation of cardiac mesoderm in mouse embryonic stem cells.

Sladecek S, Radaszkiewicz K, Bohmova M, Gybel T, Radaszkiewicz T, Pachernik J PLoS One. 2022; 17(10):e0275860.

PMID: 36227898 PMC: 9560500. DOI: 10.1371/journal.pone.0275860.

References
1.
Patterson K, Brummer T, OBrien P, Daly R . Dual-specificity phosphatases: critical regulators with diverse cellular targets. Biochem J. 2009; 418(3):475-89. DOI: 10.1042/bj20082234. View

2.
Zhang Y, Wu J, Wang Z . A distinct interaction mode revealed by the crystal structure of the kinase p38α with the MAPK binding domain of the phosphatase MKP5. Sci Signal. 2012; 4(204):ra88. DOI: 10.1126/scisignal.2002241. View

3.
Zhou G, Denu J, Wu L, Dixon J . The catalytic role of Cys124 in the dual specificity phosphatase VHR. J Biol Chem. 1994; 269(45):28084-90. View

4.
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

5.
Blaskovich M . Drug discovery and protein tyrosine phosphatases. Curr Med Chem. 2009; 16(17):2095-176. DOI: 10.2174/092986709788612693. View