Crystal structure studies of NADP+ dependent isocitrate dehydrogenase from Thermus thermophilus exhibiting a novel terminal domain.
NADP(+) dependent isocitrate dehydrogenase (IDH) is an enzyme catalyzing oxidative decarboxylation of isocitrate into oxalosuccinate (intermediate) and finally the product α-ketoglutarate. The crystal structure of Thermus thermophilus isocitrate dehydrogenase (TtIDH) ternary complex with citrate and cofactor NADP(+) was determined using X-ray diffraction method to a resolution of 1.80 Å. The overall fold of this protein was resolved into large domain, small domain and a clasp domain. The monomeric structure reveals a novel terminal domain involved in dimerization, very unique and novel domain when compared to other IDH's. And, small domain and clasp domain showing significant differences when compared to other IDH's of the same sub-family. The structure of TtIDH reveals the absence of helix at the clasp domain, which is mainly involved in oligomerization in other IDH's. Also, helices/beta sheets are absent in the small domain, when compared to other IDH's of the same sub family. The overall TtIDH structure exhibits closed conformation with catalytic triad residues, Tyr144-Asp248-Lys191 are conserved. Oligomerization of the protein is quantized using interface area and subunit-subunit interactions between protomers. Overall, the TtIDH structure with novel terminal domain may be categorized as a first structure of subfamily of type IV.
Department of Studies in Physics, University of Mysore, Mysore 570 006, India.
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SM
Kumar
Department of Studies in Microbiology, University of Mysore, Mysore 570 006, India.
K J
KJ
Pampa
Department of Studies in Physics, University of Mysore, Mysore 570 006, India.
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M
Manjula
Department of Physics, Faculty of Science, An-Najah National University, Nablus, West Bank, Palestine.
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MM
Abdoh
Advanced Protein Crystallography Research Group, RIKEN SPring-8 Center, Harima Institute, Hyogo 679-5148, Japan.
Naoki
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Kunishima
Department of Studies in Physics, University of Mysore, Mysore 570 006, India. Electronic address: lokanath@physics.uni-mysore.ac.in.
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NK
Lokanath
D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D003460:Crystallization; D007521:Isocitrate Dehydrogenase / Q000737:chemistry* / Q000648:ultrastructure*; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D016963:Thermus thermophilus / Q000201:enzymology*
D007521:Isocitrate Dehydrogenase; C039355:isocitrate dehydrogenase (NADP+)
Citrate; Metal ion; NADP(+) binding loop; Oligomerization; Unique terminal domain