Open AccessStructure of the β‐form of human MK2 in complex with the non‐selective kinase inhibitor TEI‐L03090
Author(s) -
Fujino Aiko,
Fukushima Kei,
Kubota Takaharu,
Matsumoto Yoshiyuki,
TakimotoKamimura Midori
Publication year - 2013
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
ISSN - 1744-3091
DOI - 10.1107/s1744309113030534
Subject(s) - chemistry , protein kinase a , kinase , cyclin dependent kinase 2 , map kinase kinase kinase , map2k7 , mitogen activated protein kinase kinase , p38 mitogen activated protein kinases , microbiology and biotechnology , c raf , mitogen activated protein kinase , cyclin dependent kinase 9 , biochemistry , biology
Mitogen‐activated protein kinase‐activated protein kinase 2 (MK2 or MAPKAP‐K2), a serine/threonine kinase from the p38 mitogen‐activated protein kinase signalling pathway, plays an important role in the production of TNF‐α and other cytokines. In a previous report, it was shown that MK2 in complex with the selective inhibitor TEI‐I01800 adopts an α‐helical glycine‐rich loop that is induced by the stable nonplanar conformer of TEI‐I01800. To understand the mechanism of the structural change, the structure of MK2 bound to TEI‐L03090, which lacks the key substituent found in TEI‐I01800, was determined. MK2–TEI‐L03090 has a β‐sheet glycine‐rich loop in common with other kinases, as predicted. This result suggests that a small compound can induce a drastic conformational change in the target protein structure and can be used to design potent and selective inhibitors.