2hw7
From Proteopedia
|
Crystal Structure of Mnk2-D228G in complex with Staurosporine
Overview
Autoinhibition is a recurring mode of protein kinase regulation and can be, based on diverse molecular mechanisms. Here, we show by crystal structure, analysis, nuclear magnetic resonance (NMR)-based nucleotide affinity, studies and rational mutagenesis that nonphosphorylated mitogen-activated, protein (MAP) kinases interacting kinase (Mnk) 1 is autoinhibited by, conversion of the activation segment into an autoinhibitory module. In a, Mnk1 crystal structure, the activation segment is repositioned via a, Mnk-specific sequence insertion at the N-terminal lobe with the following, consequences: (i) the peptide substrate binding site is deconstructed, (ii) the interlobal cleft is narrowed, (iii) an essential Lys-Glu pair is, disrupted and (iv) the magnesium-binding loop is locked into an, ATP-competitive conformation. Consistently, deletion of the Mnk-specific, insertion or removal of a conserved phenylalanine side chain, which, induces a blockade of the ATP pocket, increase the ATP affinity of Mnk1., Structural rearrangements required for the activation of Mnks are apparent, from the cocrystal structure of a Mnk2 D228G -staurosporine complex and, can be modeled on the basis of crystal packing interactions. Our data, suggest a novel regulatory mechanism specific for the Mnk subfamily.
About this Structure
2HW7 is a Single protein structure of sequence from Homo sapiens with ZN and STU as ligands. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
Reference
Mitogen-activated protein kinases interacting kinases are autoinhibited by a reprogrammed activation segment., Jauch R, Cho MK, Jakel S, Netter C, Schreiter K, Aicher B, Zweckstetter M, Jackle H, Wahl MC, EMBO J. 2006 Sep 6;25(17):4020-32. Epub 2006 Aug 17. PMID:16917500
Page seeded by OCA on Mon Nov 12 22:37:27 2007
