View source for 1zy5

[[Image:1zy5.gif|left|200px]]<br /><applet load="1zy5" size="450" color="white" frame="true" align="right" spinBox="true" 
caption="1zy5, resolution 2.00&Aring;" />
'''Crystal Structure of eIF2alpha Protein Kinase GCN2: R794G Hyperactivating Mutant Complexed with AMPPNP.'''<br />

==Overview==
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.

==About this Structure==
1ZY5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with MG and ANP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ZY5 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15964839 15964839]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Single protein]]
[[Category: Burley, S.K.]]
[[Category: Hinnebusch, A.G.]]
[[Category: Padyana, A.K.]]
[[Category: Qiu, H.]]
[[Category: Roll-Mecak, A.]]
[[Category: ANP]]
[[Category: MG]]
[[Category: amino-acid starvation]]
[[Category: eif2alpha kinase]]
[[Category: protein kinase]]
[[Category: signal transduction]]
[[Category: starvation stress response]]
[[Category: translation regulator]]

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