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Disease-Causing Mutations Alter the Interplay Between Loop Dynamics and Catalysis in the Protein Tyrosine Phosphatases SHP-1 and SHP-2
bioRxiv · · Preprint · Open access
Brownless, Maghsoud + 2 more
Abstract ↗AI summary
The abstract is read at the publisher; the summary is JClub's.
Disease-causing mutations in full-length and catalytic-domain-only SHP-1 and SHP-2 alter WPD-loop dynamics, disrupting the active site and negatively impacting catalysis.
- Why it matters: Autoinhibition and SH2-mediated regulation have dominated studies of these drug targets, leaving how the catalytic WPD-loop moves under oncogenic variation less understood.
- What they did: Using detailed computational simulations, the authors compared wild-type and mutant SHP-1 and SHP-2 (full-length and catalytic domain only) to map how oncogenic residues affect WPD-loop motion and catalytic performance.
- The result: Many oncogenic residues lie on allosteric pathways controlling WPD-loop dynamics, and the simulations reveal how SH2-domain presence links to loop motion differently in SHP-1 versus SHP-2.
The findingWhy it mattersWhat they didThe result
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- Open access
- 1 cites