View source for 8s39


==Crystal structure of Medicago truncatula glutamate dehydrogenase 2 in complex with isophthalic acid and NAD==
<StructureSection load='8s39' size='340' side='right'caption='[[8s39]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8s39]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Medicago_truncatula Medicago truncatula]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8S39 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8S39 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</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=8s39 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8s39 OCA], [https://pdbe.org/8s39 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8s39 RCSB], [https://www.ebi.ac.uk/pdbsum/8s39 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8s39 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/G7JYL4_MEDTR G7JYL4_MEDTR] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Glutamate dehydrogenases (GDHs) are key enzymes at the crossroads of N and C metabolism in plants. Legumes, whose N metabolism is particularly intricate, possess a unique type of GDH. This study presents an analysis of a legume-type GDH (isoform 2) from Medicago truncatula (MtGDH2). We measured MtGDH2 activity in both the Glu --&gt; 2-oxoglutarate (2OG) and 2OG --&gt; Glu reaction directions and obtained kinetic parameters for Glu, 2OG, NAD(+), and NADH. Inhibition assays revealed that compounds possessing di- or tricarboxylates act as inhibitors of plant GDHs. Interestingly, 2,6-pyridinedicarboxylate (PYR) weakly inhibits MtGDH2 compared to Arabidopsis thaliana homologs. Furthermore, we explored tetrazole derivatives to discover 3-(1H-tetrazol-5-yl)benzoic acid (TBA) as an MtGDH2 inhibitor. The kinetic experiments are supported by six crystal structures, solved as: (i) unliganded enzyme, (ii) trapping the reaction intermediate 2-amino-2-hydroxyglutarate and NAD(+), and also complexed with NAD(+) and inhibitors such as (iii) citrate, (iv) PYR, (v) isophthalate, and (vi) TBA. The complex with TBA revealed a new mode of action that, in contrast to other inhibitors, prevents domain closure. This discovery points to TBA as a starting point for the development of novel GDH inhibitors to study the functions of GDH in plants and potentially boost biomass production.

Legume-type glutamate dehydrogenase: Structure, activity, and inhibition studies.,Grzechowiak M, Sliwiak J, Link A, Ruszkowski M Int J Biol Macromol. 2024 Aug 12;278(Pt 2):134648. doi: , 10.1016/j.ijbiomac.2024.134648. PMID:39142482<ref>PMID:39142482</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8s39" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Medicago truncatula]]
[[Category: Grzechowiak M]]
[[Category: Ruszkowski M]]