1ika

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spinqualitylabelsall models 1ika, resolution 2.7Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

Overview

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.

About this Structure

1IKA is a Single protein structure of sequence from Escherichia coli with CA and AKG as ligands. Active as Isocitrate dehydrogenase (NADP(+)), with EC number 1.1.1.42 Full crystallographic information is available from OCA.

Reference

Structure of isocitrate dehydrogenase with alpha-ketoglutarate at 2.7-A resolution: conformational changes induced by decarboxylation of isocitrate., Stoddard BL, Koshland DE Jr, Biochemistry. 1993 Sep 14;32(36):9317-22. PMID:8369301

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