2hw7

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[[Image:2hw7.gif|left|200px]]
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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'''
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===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.
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(as it appears on PubMed at http://www.pubmed.gov), where 16917500 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16917500}}
==About this Structure==
==About this Structure==
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[[Category: Phosphorylation]]
[[Category: Phosphorylation]]
[[Category: Protein kinase]]
[[Category: Protein kinase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 06:47:15 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 15:10:22 2008''

Revision as of 12:10, 29 July 2008

Image:2hw7.png

Template:STRUCTURE 2hw7

Crystal Structure of Mnk2-D228G in complex with Staurosporine

Template:ABSTRACT PUBMED 16917500

About this Structure

2HW7 is a Single protein structure of sequence from Homo sapiens. 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

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