2. Academic Validation
  3. Dual function of protein phosphatase 5 (PPP5C): An emerging therapeutic target for drug discovery

Dual function of protein phosphatase 5 (PPP5C): An emerging therapeutic target for drug discovery

  • Eur J Med Chem. 2023 Jun 5:254:115350. doi: 10.1016/j.ejmech.2023.115350.
Hengheng Zhang 1,  Qiuyue Zhang 1,  Jiaqi Tu 1,  Qidong You 2,  Lei Wang 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.
  • 2 State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. Electronic address: youqd@163.com.
  • 3 State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. Electronic address: leiwang.91@cpu.edu.cn.
PMID: 37054560 DOI: 10.1016/j.ejmech.2023.115350
Abstract

Phosphorylation of proteins is reversibly controlled by the kinases and phosphatases in many posttranslational regulation patterns. Protein Phosphatase 5 (PPP5C) is a serine/threonine protein Phosphatase showing dual function by simultaneously exerting dephosphorylation and co-chaperone functions. Due to this special role, PPP5C was found to participate in many signal transductions related to various diseases. Abnormal expression of PPP5C results in cancers, obesity, and Alzheimer's disease, making it a potential drug target. However, the design of small molecules targeting PPP5C is struggling due to its special monomeric Enzyme form and low basal activity by a self-inhibition mechanism. Through realizing the PPP5C's dual function as Phosphatase and co-chaperone, more and more small molecules were found to regulate PPP5C with a different mechanism. This review aims to provide insights into PPP5C's dual function from structure to function, which could provide efficient design strategies for small molecules targeting PPP5C as therapeutic candidates.

Keywords

Dual function; PPP5C; Small molecule modulators of PPP5C; Various diseases.

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