5xjv
From Proteopedia
Two intermediate states of conformation switch in dual specificity phosphatase 13a
Structural highlights
FunctionDS13A_HUMAN Probable protein tyrosine phosphatase. Has a phosphatase activity-independent regulatory role in MAP3K5/ASK1-mediated apoptosis, preventing MAP3K5/ASK1 inhibition by AKT1. Shows no phosphatase activity on MAPK1/ERK2, MAPK8/JNK, MAPK14/p38 and MAP3K5/ASK1.[1] Publication Abstract from PubMedDual specificity phosphatases (DUSPs) include MAP kinase phosphatases and atypical dual specificity phosphatases and mediate cell growth and differentiation, brain function, and immune responses. They serve as targets for drug development against cancers, diabetes and depression. Several DUSPs have non-canonical conformation of the central beta-sheet and active site loops, suggesting that they may have conformational switch that is related to the regulation of enzyme activity. Here, we determined the crystal structure of DUSP13a, and identified two different structures that represent intermediates of the postulated conformational switch. Amino acid sequence of DUSP13a is not significantly homologous to DUSPs with conformational switch, indicating that the conformational switch is not sequence-dependent, but rather determined by ligand interaction. The sequence-independency suggests that other DUSPs with canonical conformation may have the conformational switch during specific cellular regulation. The conformational switch leads to significant changes in the protein surface, including a hydrophobic surface and pockets, which can be exploited for development of allosteric modulators of drug target DUSPs. Two intermediate states of the conformational switch in dual specificity phosphatase 13a.,Wei CH, Min HG, Kim M, Kim GH, Chun HJ, Ryu SE Pharmacol Res. 2018 Feb;128:211-219. doi: 10.1016/j.phrs.2017.10.006. Epub 2017, Oct 27. PMID:29106959[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Homo sapiens | Large Structures | Chun HJ | Min HG | Ryu SE | Wei CH