2D4V

Crystal structure of NAD dependent isocitrate dehydrogenase from Acidithiobacillus thiooxidans

Summary for 2D4V

• Entry DOI: 10.2210/pdb2d4v/pdb
• Descriptor: isocitrate dehydrogenase, CITRATE ANION, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (4 entities in total)
• Functional Keywords: alpha and beta protein, isocitrate/isopropylmalate dehydrogenase-like fold, oxidoreductase
• Biological source: Acidithiobacillus thiooxidans
• Total number of polymer chains: 4
• Total formula weight: 188481.24

Authors

Imada, K.,Tamura, T.,Namba, K.,Inagaki, K. (deposition date: 2005-10-24, release date: 2006-11-14, Last modification date: 2024-03-13)

Primary citation

Imada, K.,Tamura, T.,Takenaka, R.,Kobayashi, I.,Namba, K.,Inagaki, K.
Structure and quantum chemical analysis of NAD+-dependent isocitrate dehydrogenase: hydride transfer and co-factor specificity
Proteins, 70:63-71, 2008

PubMed Abstract: The crystal structure of Acidithiobacillus thiooxidans isocitrate dehydrogenase complexed with NAD+ and citrate has been solved to a resolution of 1.9 A. The protein fold of this NAD+-dependent enzyme shares a high similarity with those of NADP+-dependent bacterial ICDHs. The NAD+ and the citrate are clearly identified in the active site cleft with a well-defined electron density. Asp-357 is the direct cofactor-specificity determinant that interacts with 2'-OH and 3'-OH of the adenosine ribose. The adenosine ribose takes a C2'-endo puckering conformation as previously reported for an NAD+-specific isopropylmalate dehydrogenase. The nicotinamide moiety of NAD+ has the amide NH2 group oriented in cis conformation with respect to the C4 carbon of the nicotinamide ring, slanted toward the bound citrate molecule with a dihedral angle of -21 degrees . The semi-empirical molecular orbital calculation suggests that the pro-R hydrogen atom at C4 of NADH would bear the largest negative charge when the amide NH2 group is in such conformation, suggesting that the amide group has a catalytically significant role in stabilizing the transition state as NADH is being formed during the hydride transfer catalysis.

PubMed: 17634983
DOI: 10.1002/prot.21486

Experimental method

X-RAY DIFFRACTION (1.9 Å)