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Structure of the β‐form of human MK2 in complex with the non‐selective kinase inhibitor TEI‐L03090

Structure of the β‐form of human MK2 in complex with the non‐selective kinase inhibitor TEI‐L03090 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Acta Crystallographica Section F Wiley

Structure of the β‐form of human MK2 in complex with the non‐selective kinase inhibitor TEI‐L03090

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References (25)

Publisher
Wiley
Copyright
International Union of Crystallography, 2013
ISSN
1744-3091
eISSN
1744-3091
DOI
10.1107/S1744309113030534
pmid
24316826
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

Acta Crystallographica Section F – Wiley

Published: Dec 1, 2013

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