Dual Specificity Phosphatase 5-Substrate Interaction: A Mechanistic Perspective. Compr Physiol 2017 Sep 12;7(4):1449-1461
Date
09/16/2017Pubmed ID
28915331DOI
10.1002/cphy.c170007Scopus ID
2-s2.0-85045328175 (requires institutional sign-in at Scopus site) 18 CitationsAbstract
The mammalian genome contains approximately 200 phosphatases that are responsible for catalytically removing phosphate groups from proteins. In this review, we discuss dual specificity phosphatase 5 (DUSP5). DUSP5 belongs to the dual specificity phosphatase (DUSP) family, so named after the family members' abilities to remove phosphate groups from serine/threonine and tyrosine residues. We provide a comparison of DUSP5's structure to other DUSPs and, using molecular modeling studies, provide an explanation for DUSP5's mechanistic interaction and specificity toward phospho-extracellular regulated kinase, its only known substrate. We also discuss new insights from molecular modeling studies that will influence our current thinking of mitogen-activated protein kinase signaling. Finally, we discuss the lessons learned from identifying small molecules that target DUSP5, which might benefit targeting efforts for other phosphatases. © 2017 American Physiological Society. Compr Physiol 7:1449-1461, 2017.
Author List
Kutty RG, Talipov MR, Bongard RD, Lipinski RAJ, Sweeney NL, Sem DS, Rathore R, Ramchandran RAuthors
Rachel Jones Lipinski Research Scientist I in the Biochemistry department at Medical College of WisconsinRamani Ramchandran PhD Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBinding Sites
Dual-Specificity Phosphatases
Enzyme Inhibitors
Humans
MAP Kinase Signaling System
Molecular Docking Simulation
Protein Binding
