3mbc: Difference between revisions
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< | ==Crystal structure of monomeric isocitrate dehydrogenase from Corynebacterium glutamicum in complex with NADP== | ||
<StructureSection load='3mbc' size='340' side='right'caption='[[3mbc]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3mbc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Corynebacterium_glutamicum_ATCC_13032 Corynebacterium glutamicum ATCC 13032]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MBC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MBC 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]] 1.9Å</td></tr> | |||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></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=3mbc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mbc OCA], [https://pdbe.org/3mbc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mbc RCSB], [https://www.ebi.ac.uk/pdbsum/3mbc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mbc ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/IDH_CORGL IDH_CORGL] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Isocitrate dehydrogenase catalyzes the first oxidative and decarboxylation steps in the citric acid cycle. It also lies at a crucial bifurcation point between CO2-generating steps in the cycle and carbon-conserving steps in the glyoxylate bypass. Hence, the enzyme is a focus of regulation. The bacterial enzyme is typically dependent on the coenzyme nicotinamide adenine dinucleotide phosphate. The monomeric enzyme from Corynebacterium glutamicum is highly specific towards this coenzyme and the substrate isocitrate while retaining a high overall efficiency. Here, a 1.9 A resolution crystal structure of the enzyme in complex with its coenzyme and the cofactor Mg2+ is reported. Coenzyme specificity is mediated by interactions with the negatively charged 2'-phosphate group, which is surrounded by the side chains of two arginines, one histidine and, via a water, one lysine residue, forming ion pairs and hydrogen bonds. Comparison with a previous apoenzyme structure indicates that the binding site is essentially preconfigured for coenzyme binding. In a second enzyme molecule in the asymmetric unit negatively charged aspartate and glutamate residues from a symmetry-related enzyme molecule interact with the positively charged arginines, abolishing coenzyme binding. The holoenzyme from C. glutamicum displays a 36 degrees interdomain hinge-opening movement relative to the only previous holoenzyme structure of the monomeric enzyme: that from Azotobacter vinelandii. As a result, the active site is not blocked by the bound coenzyme as in the closed conformation of the latter, but is accessible to the substrate isocitrate. However, the substrate-binding site is disrupted in the open conformation. Hinge points could be pinpointed for the two molecules in the same crystal, which show a 13 degrees hinge-bending movement relative to each other. One of the two pairs of hinge residues is intimately flanked on both sides by the isocitrate-binding site. This suggests that binding of a relatively small substrate (or its competitive inhibitors) in tight proximity to a hinge point could lead to large conformational changes leading to a closed, presumably catalytically active (or inactive), conformation. It is possible that the small-molecule concerted inhibitors glyoxylate and oxaloacetate similarly bind close to the hinge, leading to an inactive conformation of the enzyme. | |||
Structure of a highly NADP+-specific isocitrate dehydrogenase.,Sidhu NS, Delbaere LT, Sheldrick GM Acta Crystallogr D Biol Crystallogr. 2011 Oct;67(Pt 10):856-69. Epub 2011, Sep 8. PMID:21931217<ref>PMID:21931217</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3mbc" style="background-color:#fffaf0;"></div> | |||
== | |||
==See Also== | ==See Also== | ||
*[[Isocitrate dehydrogenase]] | *[[Isocitrate dehydrogenase 3D structures|Isocitrate dehydrogenase 3D structures]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
[[Category: Corynebacterium glutamicum]] | </StructureSection> | ||
[[Category: | [[Category: Corynebacterium glutamicum ATCC 13032]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Aich S]] | |||
[[Category: Delbaere LTJ]] | |||
[[Category: | [[Category: Sheldrick GM]] | ||
[[Category: | [[Category: Sidhu NS]] | ||
[[Category: | |||
Latest revision as of 11:50, 6 September 2023
Crystal structure of monomeric isocitrate dehydrogenase from Corynebacterium glutamicum in complex with NADPCrystal structure of monomeric isocitrate dehydrogenase from Corynebacterium glutamicum in complex with NADP
Structural highlights
FunctionPublication Abstract from PubMedIsocitrate dehydrogenase catalyzes the first oxidative and decarboxylation steps in the citric acid cycle. It also lies at a crucial bifurcation point between CO2-generating steps in the cycle and carbon-conserving steps in the glyoxylate bypass. Hence, the enzyme is a focus of regulation. The bacterial enzyme is typically dependent on the coenzyme nicotinamide adenine dinucleotide phosphate. The monomeric enzyme from Corynebacterium glutamicum is highly specific towards this coenzyme and the substrate isocitrate while retaining a high overall efficiency. Here, a 1.9 A resolution crystal structure of the enzyme in complex with its coenzyme and the cofactor Mg2+ is reported. Coenzyme specificity is mediated by interactions with the negatively charged 2'-phosphate group, which is surrounded by the side chains of two arginines, one histidine and, via a water, one lysine residue, forming ion pairs and hydrogen bonds. Comparison with a previous apoenzyme structure indicates that the binding site is essentially preconfigured for coenzyme binding. In a second enzyme molecule in the asymmetric unit negatively charged aspartate and glutamate residues from a symmetry-related enzyme molecule interact with the positively charged arginines, abolishing coenzyme binding. The holoenzyme from C. glutamicum displays a 36 degrees interdomain hinge-opening movement relative to the only previous holoenzyme structure of the monomeric enzyme: that from Azotobacter vinelandii. As a result, the active site is not blocked by the bound coenzyme as in the closed conformation of the latter, but is accessible to the substrate isocitrate. However, the substrate-binding site is disrupted in the open conformation. Hinge points could be pinpointed for the two molecules in the same crystal, which show a 13 degrees hinge-bending movement relative to each other. One of the two pairs of hinge residues is intimately flanked on both sides by the isocitrate-binding site. This suggests that binding of a relatively small substrate (or its competitive inhibitors) in tight proximity to a hinge point could lead to large conformational changes leading to a closed, presumably catalytically active (or inactive), conformation. It is possible that the small-molecule concerted inhibitors glyoxylate and oxaloacetate similarly bind close to the hinge, leading to an inactive conformation of the enzyme. Structure of a highly NADP+-specific isocitrate dehydrogenase.,Sidhu NS, Delbaere LT, Sheldrick GM Acta Crystallogr D Biol Crystallogr. 2011 Oct;67(Pt 10):856-69. Epub 2011, Sep 8. PMID:21931217[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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