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| {{STRUCTURE_2hw7| PDB=2hw7 | SCENE= }} | | {{STRUCTURE_2hw7| PDB=2hw7 | SCENE= }} |
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| '''Crystal Structure of Mnk2-D228G in complex with Staurosporine'''
| | ===Crystal Structure of Mnk2-D228G in complex with Staurosporine=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_16917500}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 16917500 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_16917500}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Phosphorylation]] | | [[Category: Phosphorylation]] |
| [[Category: Protein kinase]] | | [[Category: Protein kinase]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 06:47:15 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 15:10:22 2008'' |
