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'''Structure of human glutamate dehydrogenase-apo form''' | '''Structure of human glutamate dehydrogenase-apo form''' | ||
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==Reference== | ==Reference== | ||
The structure of apo human glutamate dehydrogenase details subunit communication and allostery., Smith TJ, Schmidt T, Fang J, Wu J, Siuzdak G, Stanley CA, J Mol Biol. 2002 May 3;318(3):765-77. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12054821 12054821] | The structure of apo human glutamate dehydrogenase details subunit communication and allostery., Smith TJ, Schmidt T, Fang J, Wu J, Siuzdak G, Stanley CA, J Mol Biol. 2002 May 3;318(3):765-77. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12054821 12054821] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: Stanley, C A.]] | [[Category: Stanley, C A.]] | ||
[[Category: Wu, J.]] | [[Category: Wu, J.]] | ||
[[Category: | [[Category: Allostery]] | ||
[[Category: | [[Category: Negative cooperativity]] | ||
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Revision as of 23:25, 2 May 2008
Structure of human glutamate dehydrogenase-apo form
OverviewOverview
The structure of human glutamate dehydrogenase (GDH) has been determined in the absence of active site and regulatory ligands. Compared to the structures of bovine GDH that were complexed with coenzyme and substrate, the NAD binding domain is rotated away from the glutamate-binding domain. The electron density of this domain is more disordered the further it is from the pivot helix. Mass spectrometry results suggest that this is likely due to the apo form being more dynamic than the closed form. The antenna undergoes significant conformational changes as the catalytic cleft opens. The ascending helix in the antenna moves in a clockwise manner and the helix in the descending strand contracts in a manner akin to the relaxation of an extended spring. A number of spontaneous mutations in this antenna region cause the hyperinsulinism/hyperammonemia syndrome by decreasing GDH sensitivity to the inhibitor, GTP. Since these residues do not directly contact the bound GTP, the conformational changes in the antenna are apparently crucial to GTP inhibition. In the open conformation, the GTP binding site is distorted such that it can no longer bind GTP. In contrast, ADP binding benefits by the opening of the catalytic cleft since R463 on the pivot helix is pushed into contact distance with the beta-phosphate of ADP. These results support the previous proposal that purines regulate GDH activity by altering the dynamics of the NAD binding domain. Finally, a possible structural mechanism for negative cooperativity is presented.
About this StructureAbout this Structure
1L1F is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
The structure of apo human glutamate dehydrogenase details subunit communication and allostery., Smith TJ, Schmidt T, Fang J, Wu J, Siuzdak G, Stanley CA, J Mol Biol. 2002 May 3;318(3):765-77. PMID:12054821 Page seeded by OCA on Fri May 2 23:25:48 2008