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Dual Specificity Phosphatase 5-Substrate Interaction: A Mechanistic Perspective. Compr Physiol 2017 Sep 12;7(4):1449-1461

Date

09/16/2017

Pubmed ID

28915331

DOI

10.1002/cphy.c170007

Abstract

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 R

Author

Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Binding Sites
Dual-Specificity Phosphatases
Enzyme Inhibitors
Humans
MAP Kinase Signaling System
Molecular Docking Simulation
Protein Binding
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d