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) 15 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 RAuthor
Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of WisconsinMESH 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