1IKA

STRUCTURE OF ISOCITRATE DEHYDROGENASE WITH ALPHA-KETOGLUTARATE AT 2.7 ANGSTROMS RESOLUTION: CONFORMATIONAL CHANGES INDUCED BY DECARBOXYLATION OF ISOCITRATE

Summary for 1IKA

• Entry DOI: 10.2210/pdb1ika/pdb
• Descriptor: ISOCITRATE DEHYDROGENASE, CALCIUM ION, 2-OXOGLUTARIC ACID (3 entities in total)
• Functional Keywords: oxidoreductase(nad(a)-choh(d))
• Biological source: Escherichia coli
• Total number of polymer chains: 1
• Total formula weight: 45995.74

Authors

Stoddard, B.L.,Koshland Junior, D.E. (deposition date: 1993-06-15, release date: 1994-07-31, Last modification date: 2024-02-07)

Primary citation

Stoddard, B.L.,Koshland Jr., D.E.
Structure of isocitrate dehydrogenase with alpha-ketoglutarate at 2.7-A resolution: conformational changes induced by decarboxylation of isocitrate.
Biochemistry, 32:9317-9322, 1993

PubMed Abstract: The structure of the isocitrate dehydrogenase (IDH) complex with bound alpha-ketoglutarate, Ca2+, and NADPH was solved at 2.7-A resolution. The alpha-ketoglutarate binds in the active site at the same position and orientation as isocitrate, with a difference between the two bound molecules of about 0.8 A. The Ca2+ metal is coordinated by alpha-ketoglutarate, three conserved aspartate residues, and a pair of water molecules. The largest motion in the active site relative to the isocitrate enzyme complex is observed for tyrosine 160, which originally forms a hydrogen bond to the labile carboxyl group of isocitrate and moves to form a new hydrogen bond to Asp 307 in the complex with alpha-ketoglutarate. This triggers a number of significant movements among several short loops and adjoining secondary structural elements in the enzyme, most of which participate in dimer stabilization and formation of the active-site cleft. These rearrangements are similar to the ligand-binding-induced movements observed in globins and insulin and serve as a model for an enzymatic mechanism which involves local shifts of secondary structural elements during turnover, rather than large-scale domain closures or loop transitions induced by substrate binding such as those observed in hexokinase or triosephosphate isomerase.

PubMed: 8369301
DOI: 10.1021/bi00087a009

Experimental method

X-RAY DIFFRACTION (2.7 Å)