P38α Mitogen-Activated Protein Kinase Is a Druggable Target in Pancreatic Adenocarcinoma.

ABSTRACT: p38 mitogen-activated protein kinases are signaling molecules with major involvement in cancer. A detailed mechanistic understanding of how p38 MAPK family members function is urgently warranted for cancer targeted therapy. The conformational dynamics of the most common member of p38 MAPK family, p38α, are crucial for its function but poorly understood. Here we found that, unlike in other cancer types, p38α is significantly activated in pancreatic adenocarcinoma samples, suggesting its potential for anti-pancreatic cancer therapy. Using a state of the art supercomputer, Anton, long-timescale (39 μs) unbiased molecular dynamics simulations of p38α show that apo p38α has high structural flexibility in six regions, and reveal potential catalysis mechanism involving a "butterfly" motion. Moreo

SUBMITTER: Yang L 

PROVIDER: S-EPMC6890821 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature