View source for 6dhl


==Bovine glutamate dehydrogenase complexed with epicatechin-3-gallate (ECG)==
<StructureSection load='6dhl' size='340' side='right'caption='[[6dhl]], [[Resolution|resolution]] 3.62&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6dhl]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3mvq 3mvq]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DHL OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6DHL FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=XEG:(2R,3S)-2-(3,4-DIHYDROXYPHENYL)-5,7-DIHYDROXY-3,4-DIHYDRO-2H-CHROMEN-3-YL+3,4,5-TRIHYDROXYBENZOATE'>XEG</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glutamate_dehydrogenase Glutamate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.4.1.2 1.4.1.2] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6dhl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dhl OCA], [http://pdbe.org/6dhl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dhl RCSB], [http://www.ebi.ac.uk/pdbsum/6dhl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dhl ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Glutamate dehydrogenase (GDH) catalyzes the oxidative deamination of L-glutamate and, in animals, is extensively regulated by a number of metabolites. Gain of function mutations in GDH that abrogate GTP inhibition causes the hyperinsulinism/hyperammonemia syndrome (HHS), resulting in increased pancreatic beta-cells responsiveness to leucine and susceptibility to hypoglycemia following high protein meals. We have previously shown that two of the polyphenols from green tea (EGCG and ECG) inhibit GDH in-vitro and that EGCG blocks GDH-mediated insulin secretion in wild type rat islets. Using structural and site-directed mutagenesis studies, we demonstrate that ECG binds to the same site as the allosteric regulator, ADP. Perifusion assays using pancreatic islets from transgenic mice expressing a human HHS form of GDH demonstrate that the hyper-response to glutamine caused by dysregulated GDH is blocked by the addition of EGCG. As observed in HHS patients, these transgenic mice are hypersensitive to amino acid feeding and this is abrogated by oral administration of EGCG prior to challenge. Finally, the low basal blood glucose level in the HHS mouse model is improved upon chronic administration of EGCG. These results suggest that this common natural product, or some derivative thereof, may prove useful in controlling this genetic disorder. Of broader clinical implication is that other groups have shown restriction of glutamine catabolism via these GDH inhibitors can be useful in treating various tumors. This HHS transgenic mouse model offers a highly useful means to test these agents in-vivo.

GREEN TEA POLYPHENOLS CONTROL DYSREGULATED GLUTAMATE DEHYDROGENASE IN TRANSGENIC MICE BY HIJACKING THE ADP ACTIVATION SITE.,Li C, Li M, Chen P, Narayan S, Matschinsky FM, Bennett MJ, Stanley C, Smith TJ J Biol Chem. 2011 Aug 3. PMID:21813650<ref>PMID:21813650</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6dhl" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glutamate dehydrogenase 3D structures|Glutamate dehydrogenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Glutamate dehydrogenase]]
[[Category: Large Structures]]
[[Category: Smith, T J]]
[[Category: Dehydrogenase]]
[[Category: Ecg]]
[[Category: Glutamate]]
[[Category: Inhibition]]
[[Category: Oxidoreductase]]