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Conformational Dynamics of Deubiquitinase A and Functional Implications

Biochemistry. 2021-01; 
Ashish Kabra, Ying Li
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Mutagenesis Services The R272E/K273E mutant was generated using the mutagenesis service of Genscript. 2H- and 15N-labeled DUBA samples were prepared according to the previously reported methods. Get A Quote

摘要

Deubiquitinase A (DUBA) belongs to the ovarian tumor family of deubiquitinating enzymes and was initially identified as a negative regulator of type I interferons, whose overproduction has been linked to autoimmune diseases. The deubiquitinating activity of DUBA is positively regulated by phosphorylation at a single serine residue, S177, which results in minimal structural changes. We have previously shown that phosphorylation induces a two-state conformational equilibrium observed only in the active form of DUBA, highlighting the functional importance of DUBA dynamics. Here, we report the conformational dynamics of DUBA on the microsecond-to-millisecond time scales characterized by nuclear magnetic resonance r... More

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