Crystal Structure of the Human LIMK2 Kinase Domain In Complex With a Non-ATP Competitive Inhibitor

Discovery of a Type III Inhibitor of LIM Kinase 2 That Binds in a DFG-Out Conformation.

DLIHGEVLGKGFFGQAIKVTHKATGKVMVMKELIRCDEETQKTFLTEVKVMRSLDHPNVLKFIGVLYKDKKLNLLTEYIE
GGTLKDFLRSMDPFPWQQKVRFAKGIASGMAYLHSMCIIHRDLNSHNCLIKLDKTVVVADFGLSRLIVEERKRAPMEKAT
TKKRTLRKNDRKKRYTVVGNPYWMAPEMLNGKSYDETVDIFSFGIVLCEIIGQVYADPDCLPRTLDFGLNVKLFWEKFVP
TDCPPAFFPLAAICCRLEPESRPAFSKLEDSFEALSLYLGELGIPLPAELEELDHTVSMQYGL

The purified protein was used in crystallisation trials employing both, a standard screen with approximately 1200 different conditions, as well as crystallisation conditions identified using literature data.

HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS

LIMK2 KINASE, DFG INHIBITOR, TRANSFERASE-TRANSFERASE INHIBITOR complex