1zy4

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{{STRUCTURE_1zy4| PDB=1zy4 | SCENE= }}
{{STRUCTURE_1zy4| PDB=1zy4 | SCENE= }}
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'''Crystal Structure of eIF2alpha Protein Kinase GCN2: R794G Hyperactivating Mutant in Apo Form.'''
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===Crystal Structure of eIF2alpha Protein Kinase GCN2: R794G Hyperactivating Mutant in Apo Form.===
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==Overview==
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The GCN2 protein kinase coordinates protein synthesis with levels of amino acid stores by phosphorylating eukaryotic translation initiation factor 2. The autoinhibited form of GCN2 is activated in cells starved of amino acids by binding of uncharged tRNA to a histidyl-tRNA synthetase-like domain. Replacement of Arg-794 with Gly in the PK domain (R794G) activates GCN2 independently of tRNA binding. Crystal structures of the GCN2 protein kinase domain have been determined for wild-type and R794G mutant forms in the apo state and bound to ATP/AMPPNP. These structures reveal that GCN2 autoinhibition results from stabilization of a closed conformation that restricts ATP binding. The R794G mutant shows increased flexibility in the hinge region connecting the N- and C-lobes, resulting from loss of multiple interactions involving Arg794. This conformational change is associated with intradomain movement that enhances ATP binding and hydrolysis. We propose that intramolecular interactions following tRNA binding remodel the hinge region in a manner similar to the mechanism of enzyme activation elicited by the R794G mutation.
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(as it appears on PubMed at http://www.pubmed.gov), where 15964839 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15964839}}
==About this Structure==
==About this Structure==
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[[Category: Starvation stress response]]
[[Category: Starvation stress response]]
[[Category: Translation regulator]]
[[Category: Translation regulator]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 18:13:28 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 18:05:59 2008''

Revision as of 15:06, 27 July 2008

Image:1zy4.png

Template:STRUCTURE 1zy4

Crystal Structure of eIF2alpha Protein Kinase GCN2: R794G Hyperactivating Mutant in Apo Form.

Template:ABSTRACT PUBMED 15964839

About this Structure

1ZY4 is a Single protein structure of sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.

Reference

Structural basis for autoinhibition and mutational activation of eukaryotic initiation factor 2alpha protein kinase GCN2., Padyana AK, Qiu H, Roll-Mecak A, Hinnebusch AG, Burley SK, J Biol Chem. 2005 Aug 12;280(32):29289-99. Epub 2005 Jun 17. PMID:15964839

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