This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
5k11
From Proteopedia
(Difference between revisions)
m (Protected "5k11" [edit=sysop:move=sysop]) |
|||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Cryo-EM structure of isocitrate dehydrogenase (IDH1) in inhibitor-bound state== | |
| + | <StructureSection load='5k11' size='340' side='right' caption='[[5k11]], [[Resolution|resolution]] 3.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5k11]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K11 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5K11 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5k0z|5k0z]], [[5k10|5k10]], [[5k12|5k12]]</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=5k11 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k11 OCA], [http://pdbe.org/5k11 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5k11 RCSB], [http://www.ebi.ac.uk/pdbsum/5k11 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/IDHC_HUMAN IDHC_HUMAN]] Defects in IDH1 are involved in the development of glioma (GLM) [MIM:[http://omim.org/entry/137800 137800]]. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas. Note=Mutations affecting Arg-132 are tissue-specific, and suggest that this residue plays a unique role in the development of high-grade gliomas. Mutations of Arg-132 to Cys, His, Leu or Ser abolish magnesium binding and abolish the conversion of isocitrate to alpha-ketoglutarate. Instead, alpha-ketoglutarate is converted to R(-)-2-hydroxyglutarate. Elevated levels of R(-)-2-hydroxyglutarate are correlated with an elevated risk of malignant brain tumors. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Recent advances in single-particle cryoelecton microscopy (cryo-EM) are enabling generation of numerous near-atomic resolution structures for well-ordered protein complexes with sizes >/= approximately 200 kDa. Whether cryo-EM methods are equally useful for high-resolution structural analysis of smaller, dynamic protein complexes such as those involved in cellular metabolism remains an important question. Here, we present 3.8 A resolution cryo-EM structures of the cancer target isocitrate dehydrogenase (93 kDa) and identify the nature of conformational changes induced by binding of the allosteric small-molecule inhibitor ML309. We also report 2.8-A- and 1.8-A-resolution structures of lactate dehydrogenase (145 kDa) and glutamate dehydrogenase (334 kDa), respectively. With these results, two perceived barriers in single-particle cryo-EM are overcome: (1) crossing 2 A resolution and (2) obtaining structures of proteins with sizes < 100 kDa, demonstrating that cryo-EM can be used to investigate a broad spectrum of drug-target interactions and dynamic conformational states. | ||
| - | + | Breaking Cryo-EM Resolution Barriers to Facilitate Drug Discovery.,Merk A, Bartesaghi A, Banerjee S, Falconieri V, Rao P, Davis MI, Pragani R, Boxer MB, Earl LA, Milne JL, Subramaniam S Cell. 2016 Jun 16;165(7):1698-707. doi: 10.1016/j.cell.2016.05.040. Epub 2016 May, 26. PMID:27238019<ref>PMID:27238019</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 5k11" style="background-color:#fffaf0;"></div> | |
| - | + | == References == | |
| - | + | <references/> | |
| - | + | __TOC__ | |
| + | </StructureSection> | ||
[[Category: Banerjee, S]] | [[Category: Banerjee, S]] | ||
[[Category: Bartesaghi, A]] | [[Category: Bartesaghi, A]] | ||
| + | [[Category: Earl, L]] | ||
| + | [[Category: Falconieri, V]] | ||
| + | [[Category: Merk, A]] | ||
| + | [[Category: Milne, J]] | ||
[[Category: Rao, P]] | [[Category: Rao, P]] | ||
[[Category: Subramaniam, S]] | [[Category: Subramaniam, S]] | ||
| + | [[Category: Isocitrate dehydrogenase]] | ||
| + | [[Category: Oxidoreductase]] | ||
| + | [[Category: Small metabolic complex]] | ||
| + | [[Category: Small molecule inhibitor]] | ||
Revision as of 15:28, 20 June 2016
Cryo-EM structure of isocitrate dehydrogenase (IDH1) in inhibitor-bound state
| |||||||||||
