4aj3: Difference between revisions
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==3D structure of E. coli Isocitrate Dehydrogenase in complex with Isocitrate, calcium(II) and NADP - The pseudo-Michaelis complex== | |||
<StructureSection load='4aj3' size='340' side='right' caption='[[4aj3]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4aj3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lepidoptera_sp._bold:aaa8691 Lepidoptera sp. bold:aaa8691]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AJ3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AJ3 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ICT:ISOCITRIC+ACID'>ICT</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4aja|4aja]], [[4ajb|4ajb]], [[4ajc|4ajc]], [[4ajs|4ajs]], [[4ajr|4ajr]]</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Isocitrate_dehydrogenase_(NADP(+)) Isocitrate dehydrogenase (NADP(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.42 1.1.1.42] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4aj3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aj3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4aj3 RCSB], [http://www.ebi.ac.uk/pdbsum/4aj3 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
NADP(+) dependent isocitrate dehydrogenase (IDH; EC 1.1.1.42) belongs to a large family of alpha-hydroxyacid oxidative beta-decarboxylases that catalyze similar three-step reactions, with dehydrogenation to an oxaloacid intermediate preceding beta-decarboxylation to an enol intermediate followed by tautomerization to the final alpha-ketone product. A comprehensive view of the induced fit needed for catalysis is revealed on comparing the first "fully closed" crystal structures of a pseudo-Michaelis complex of wild-type Escherichia coli IDH (EcoIDH) and the "fully closed" reaction product complex of the K100M mutant with previously obtained "quasi-closed" and "open" conformations. Conserved catalytic residues, binding the nicotinamide ring of NADP(+) and the metal-bound substrate, move as rigid bodies during domain closure by a hinge motion that spans the central beta-sheet in each monomer. Interactions established between Thr105 and Ser113, which flank the "phosphorylation loop", and the nicotinamide mononucleotide moiety of NADP(+) establish productive coenzyme binding. Electrostatic interactions of a Lys100-Leu103-Asn115-Glu336 tetrad play a pivotal role in assembling a catalytically competent active site. As predicted, Lys230* is positioned to deprotonate/reprotonate the alpha-hydroxyl in both reaction steps and Tyr160 moves into position to protonate C3 following beta-decarboxylation. A proton relay from the catalytic triad Tyr160-Asp307-Lys230* connects the alpha-hydroxyl of isocitrate to the bulk solvent to complete the picture of the catalytic mechanism. | |||
Induced fit and the catalytic mechanism of isocitrate dehydrogenase.,Goncalves S, Miller SP, Carrondo MA, Dean AM, Matias PM Biochemistry. 2012 Sep 11;51(36):7098-115. Epub 2012 Aug 27. PMID:22891681<ref>PMID:22891681</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Isocitrate dehydrogenase|Isocitrate dehydrogenase]] | *[[Isocitrate dehydrogenase|Isocitrate dehydrogenase]] | ||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Lepidoptera sp. bold:aaa8691]] | [[Category: Lepidoptera sp. bold:aaa8691]] | ||
[[Category: Carrondo, M A | [[Category: Carrondo, M A]] | ||
[[Category: Dean, A M | [[Category: Dean, A M]] | ||
[[Category: Goncalves, S | [[Category: Goncalves, S]] | ||
[[Category: Matias, P M | [[Category: Matias, P M]] | ||
[[Category: Miller, S P | [[Category: Miller, S P]] | ||
[[Category: Oxidative beta-decarboxylation]] | [[Category: Oxidative beta-decarboxylation]] | ||
[[Category: Oxidoreductase]] | [[Category: Oxidoreductase]] | ||