2B0T

Structure of Monomeric NADP Isocitrate dehydrogenase

Summary for 2B0T

• Entry DOI: 10.2210/pdb2b0t/pdb
• Related: 1ITW 1J1W
• Descriptor: NADP Isocitrate dehydrogenase, MAGNESIUM ION (3 entities in total)
• Functional Keywords: monomeric, nadp, idh, oxidoreductase
• Biological source: Corynebacterium glutamicum
• Total number of polymer chains: 1
• Total formula weight: 80191.31

Authors

Imabayashi, F.,Aich, S.,Prasad, L.,Delbaere, L.T. (deposition date: 2005-09-14, release date: 2006-01-31, Last modification date: 2024-02-14)

Primary citation

Imabayashi, F.,Aich, S.,Prasad, L.,Delbaere, L.T.
Substrate-free structure of a monomeric NADP isocitrate dehydrogenase: An open conformation phylogenetic relationship of isocitrate dehydrogenase.
Proteins, 63:100-112, 2006

PubMed Abstract: Both monomeric and dimeric NADP+-dependent isocitrate dehydrogenase (IDH) belong to the metal-dependent beta-decarboxylating dehydrogenase family and catalyze the oxidative decarboxylation from 2R,3S-isocitrate to yield 2-oxoglutarate, CO2, and NADPH. It is important to solve the structures of IDHs from various species to correlate with its function and evolutionary significance. So far, only two crystal structures of substrate/cofactor-bound (isocitrate/NADP) NADP+-dependent monomeric IDH from Azotobacter vinelandii (AvIDH) have been solved. Herein, we report for the first time the substrate/cofactor-free structure of a monomeric NADP+-dependent IDH from Corynebacterium glutamicum (CgIDH) in the presence of Mg2+. The 1.75 A structure of CgIDH-Mg2+ showed a distinct open conformation in contrast to the closed conformation of AvIDH-isocitrate/NADP+ complexes. Fluorescence studies on CgIDH in the presence of isocitrate/or NADP+ suggest the presence of low energy barrier conformers. In CgIDH, the amino acid residues corresponding to the Escherichia coli IDH phosphorylation-loop are alpha-helical compared with the more flexible random-coil region in the E. coli protein where IDH activation is controlled by phosphorylation. This more structured region supports the idea that activation of CgIDH is not controlled by phosphorylation. Monomeric NADP+-specific IDHs have been identified from about 50 different bacterial species, such as proteobacteria, actinobacteria, and planctomycetes, whereas, dimeric NADP+-dependent IDHs are diversified in both prokaryotes and eukaryotes. We have constructed a phylogenetic tree based on amino acid sequences of all bacterial monomeric NADP+-dependent IDHs and also another one with specifically chosen species which either contains both monomeric and dimeric NADP+-dependent IDHs or have monomeric NADP+-dependent, as well as NAD+-dependent IDHs. This is done to examine evolutionary relationships.

PubMed: 16416443
DOI: 10.1002/prot.20867

Experimental method

X-RAY DIFFRACTION (1.75 Å)