1J1W

Crystal Structure Of The Monomeric Isocitrate Dehydrogenase In Complex With NADP+

Summary for 1J1W

• Entry DOI: 10.2210/pdb1j1w/pdb
• Related: 1ITW
• Descriptor: Isocitrate Dehydrogenase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 entities in total)
• Functional Keywords: greek key motif, oxidoreductase
• Biological source: Azotobacter vinelandii
• Cellular location: Cytoplasm: P16100
• Total number of polymer chains: 4
• Total formula weight: 325004.15

Authors

Yasutake, Y.,Watanabe, S.,Yao, M.,Takada, Y.,Fukunaga, N.,Tanaka, I. (deposition date: 2002-12-19, release date: 2003-09-23, Last modification date: 2023-10-25)

Primary citation

Yasutake, Y.,Watanabe, S.,Yao, M.,Takada, Y.,Fukunaga, N.,Tanaka, I.
Crystal Structure of the Monomeric Isocitrate Dehydrogenase in the Presence of NADP+
J.Biol.Chem., 278:36897-36904, 2003

PubMed Abstract: NADP+-dependent monomeric isocitrate dehydrogenase (IDH) from the nitrogen-fixing bacterium Azotobacter vinelandii (AvIDH) is one of members of the beta-decarboxylating dehydrogenase family and catalyzes the dehydration and decarboxylation of isocitrate to yield 2-oxoglutrate and CO2 in the Krebs cycle. We solved the crystal structure of the AvIDH in complex with cofactor NADP+ (AvIDH-NADP+ complex). The final refined model shows the closed form that has never been detected in any previously solved structures of beta-decarboxylating dehydrogenases. The structure also reveals all of the residues that interact with NADP+. The structure-based sequence alignment reveals that these residues were not conserved in any other dimeric NADP+-dependent IDHs. Therefore the NADP+ specificity of the monomeric and dimeric IDHs was independently acquired through the evolutional process. The AvIDH was known to show an exceptionally high turnover rate. The structure of the AvIDH-NADP+ complex indicates that one loop, which is not present in the Escherichia coli IDHs, reliably stabilizes the conformation of the nicotinamide mononucleotide of the bound NADP+ by forming a few hydrogen bonds, and such interactions are considered to be important for the monomeric enzyme to initiate the hydride transfer reaction immediately. Finally, the structure of the AvIDH is compared with that of other dimeric NADP-IDHs. Several structural features demonstrate that the monomeric IDHs are structurally more related to the eukaryotic dimeric IDHs than to the bacterial dimeric IDHs.

PubMed: 12855708
DOI: 10.1074/jbc.M304091200

Experimental method

X-RAY DIFFRACTION (3.2 Å)