7ecr
From Proteopedia
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==Crystal Structure of Aspergillus terreus Glutamate Dehydrogenase (AtGDH) Complexed With Succinate and ADP-ribose== | ==Crystal Structure of Aspergillus terreus Glutamate Dehydrogenase (AtGDH) Complexed With Succinate and ADP-ribose== | ||
| - | <StructureSection load='7ecr' size='340' side='right'caption='[[7ecr]]' scene=''> | + | <StructureSection load='7ecr' size='340' side='right'caption='[[7ecr]], [[Resolution|resolution]] 1.73Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ECR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ECR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7ecr]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ECR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ECR FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7ecr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ecr OCA], [https://pdbe.org/7ecr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ecr RCSB], [https://www.ebi.ac.uk/pdbsum/7ecr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ecr ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A2R:[(2R,3R,4R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-3-HYDROXY-4-(PHOSPHONOOXY)TETRAHYDROFURAN-2-YL]METHYL+[(2R,3S,4R,5R)-3,4,5-TRIHYDROXYTETRAHYDROFURAN-2-YL]METHYL+DIHYDROGEN+DIPHOSPHATE'>A2R</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</scene></td></tr> |
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[5xvx|5xvx]]</div></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7ecr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ecr OCA], [https://pdbe.org/7ecr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ecr RCSB], [https://www.ebi.ac.uk/pdbsum/7ecr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ecr ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Glutamate dehydrogenase (GDH) is a salient metabolic enzyme which catalyzes the NAD(+) - or NADP(+) -dependent reversible conversion of alpha-ketoglutarate (AKG) to l-glutamate; and thereby connects the carbon and nitrogen metabolism cycles in all living organisms. The function of GDH is extensively regulated by both metabolites (citrate, succinate, etc.) and non-metabolites (ATP, NADH, etc.) but sufficient molecular evidences are lacking to rationalize the inhibitory effects by the metabolites. We have expressed and purified NADP(+) -dependent Aspergillus terreus GDH (AtGDH) in recombinant form. Succinate, malonate, maleate, fumarate, and tartrate independently inhibit the activity of AtGDH to different extents. The crystal structures of AtGDH complexed with the dicarboxylic acid metabolites and the coenzyme NADPH have been determined. Although AtGDH structures are not complexed with substrate; surprisingly, they acquire super closed conformation like previously reported for substrate and coenzyme bound catalytically competent Aspergillus niger GDH (AnGDH). These dicarboxylic acid metabolites partially occupy the same binding pocket as substrate; but interact with varying polar interactions and the coenzyme NADPH binds to the Domain-II of AtGDH. The low inhibition potential of tartrate as compared to other dicarboxylic acid metabolites is due to its weaker interactions of carboxylate groups with AtGDH. Our results suggest that the length of carbon skeleton and positioning of the carboxylate groups of inhibitors between two conserved lysine residues at the GDH active site might be the determinants of their inhibitory potency. Molecular details on the dicarboxylic acid metabolites bound AtGDH active site architecture presented here would be applicable to GDHs in general. | ||
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| + | Molecular insights into the inhibition of glutamate dehydrogenase by the dicarboxylic acid metabolites.,Godsora BKJ, Prakash P, Punekar NS, Bhaumik P Proteins. 2021 Nov 8. doi: 10.1002/prot.26276. PMID:34748226<ref>PMID:34748226</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7ecr" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Bhaumik P]] | + | [[Category: Bhaumik, P]] |
| - | [[Category: Godsora | + | [[Category: Godsora, B K.J]] |
| - | [[Category: Prakash P]] | + | [[Category: Prakash, P]] |
| - | [[Category: Punekar | + | [[Category: Punekar, N S]] |
| + | [[Category: Allostery]] | ||
| + | [[Category: Aspergillus]] | ||
| + | [[Category: Enzyme mechanism]] | ||
| + | [[Category: Glutamate dehydrogenase]] | ||
| + | [[Category: Oxidoreductase]] | ||
Revision as of 08:36, 23 February 2022
Crystal Structure of Aspergillus terreus Glutamate Dehydrogenase (AtGDH) Complexed With Succinate and ADP-ribose
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