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Allosteric activation of SENP1 by SUMO1 beta-grasp domain involves a dock-and-coalesce mechanism

Title: Allosteric Activation Of Senp1 By Sumo1 Beta-grasp Domain Involves A Dock-and-coalesce Mechanism.
Name(s): Guo, Jingjing, author
Zhou, Huan-Xiang, author
Type of Resource: text
Genre: Text
Date Issued: 2016-08-31
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Small ubiquitin-related modifiers (SUMOs) are conjugated to proteins to regulate a variety of cellular processes. SENPs are cysteine proteases with a catalytic center located within a channel between two subdomains that catalyzes SUMO C-terminal cleavage for processing of SUMO precursors and de-SUMOylation of target proteins. The beta-grasp domain of SUMOs binds to an exosite cleft, and allosterically activates SENPs via an unknown mechanism. Our molecular dynamics simulations showed that binding of the beta-grasp domain induces significant conformational and dynamic changes in SENP1, including widening of the exosite cleft and quenching of nanosecond dynamics in all but a distal region. A dock-and-coalesce mechanism emerges for SENP-catalyzed SUMO cleavage: the wedging of the beta-grasp domain enables the docking of the proximal portion of the C-terminus and the strengthened cross-channel motional coupling initiates inter-subdomain correlated motions to allow for the distal portion to coalesce around the catalytic center.
Identifier: FSU_libsubv1_wos_000384449900001 (IID), 10.7554/eLife.18249 (DOI)
Keywords: complex, crystal-structure, force-fields, prostate-cancer, proteases, protein allostery, rate constants, small-molecule inhibitors, structural basis, ubiquitin
Publication Note: The publisher’s version of record is available at
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Host Institution: FSU
Is Part Of: Elife.
Issue: vol. 5

Choose the citation style.
Guo, J., & Zhou, H. -X. (2016). Allosteric Activation Of Senp1 By Sumo1 Beta-grasp Domain Involves A Dock-and-coalesce Mechanism. Elife. Retrieved from