3BLV

Yeast Isocitrate Dehydrogenase with Citrate Bound in the Regulatory Subunits

Summary for 3BLV

• Entry DOI: 10.2210/pdb3blv/pdb
• Related: 3BLW 3BLX
• Descriptor: Isocitrate dehydrogenase [NAD] subunit 1, Isocitrate dehydrogenase [NAD] subunit 2, CITRATE ANION (3 entities in total)
• Functional Keywords: tca cycle, oxidative metabolism, allostery, dehydrogenase, decarboxylase, allosteric enzyme, magnesium, manganese, metal-binding, mitochondrion, nad, oxidoreductase, rna-binding, transit peptide, tricarboxylic acid cycle, phosphoprotein
• Biological source: Saccharomyces cerevisiae (baker's yeast); More
• Cellular location: Mitochondrion: P28834; Mitochondrion matrix: P28241
• Total number of polymer chains: 8
• Total formula weight: 309056.59

Authors

Taylor, A.B.,Hu, G.,Hart, P.J.,McAlister-Henn, L. (deposition date: 2007-12-11, release date: 2008-02-05, Last modification date: 2024-10-30)

Primary citation

Taylor, A.B.,Hu, G.,Hart, P.J.,McAlister-Henn, L.
Allosteric Motions in Structures of Yeast NAD+-specific Isocitrate Dehydrogenase.
J.Biol.Chem., 283:10872-10880, 2008

PubMed Abstract: Mitochondrial NAD(+)-specific isocitrate dehydrogenases (IDHs) are key regulators of flux through biosynthetic and oxidative pathways in response to cellular energy levels. Here we present the first structures of a eukaryotic member of this enzyme family, the allosteric, hetero-octameric, NAD(+)-specific IDH from yeast in three forms: 1) without ligands, 2) with bound analog citrate, and 3) with bound citrate + AMP. The structures reveal the molecular basis for ligand binding to homologous but distinct regulatory and catalytic sites positioned at the interfaces between IDH1 and IDH2 subunits and define pathways of communication between heterodimers and heterotetramers in the hetero-octamer. Disulfide bonds observed at the heterotetrameric interfaces in the unliganded IDH hetero-octamer are reduced in the ligand-bound forms, suggesting a redox regulatory mechanism that may be analogous to the "on-off" regulation of non-allosteric bacterial IDHs via phosphorylation. The results strongly suggest that eukaryotic IDH enzymes are exquisitely tuned to ensure that allosteric activation occurs only when concentrations of isocitrate are elevated.

PubMed: 18256028
DOI: 10.1074/jbc.M708719200

Experimental method

X-RAY DIFFRACTION (3.2 Å)