TY - JOUR
T1 - Ligand-induced changes in the conformation of 3-isopropylmalate dehydrogenase from Thermus thermophilus
AU - Kadono, Shojiro
AU - Sakurai, Masahiro
AU - Moriyama, Hideaki
AU - Sato, Mamoru
AU - Hayashi, Yoko
AU - Oshima, Tairo
AU - Tanaka, Nobuo
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1995/10
Y1 - 1995/10
N2 - The structures of 3-isopropylmalate dehydrogenase (IPMDH) from Thermus thermophilus in complexes with its substrate, cofactor, and a cofactor analog were investigated by X-ray diffraction in a crystalline state and by small-angle X-ray scattering (SAXS) in solution. The structures at 2.8 Å resolution of the complexes with the substrate, 3-isopropylmalate (IPM), and with an analog of NAD, ADP-ribose, were both very close to the structure of the free enzyme, which adopts an open conformation. However, the binding of a ligand induced a small conformational change near the binding site. This result contrasts with results for NADP+-bound and isocitrate-bound isocitrate dehydrogenase (ICDH) from Escherichia coli, which adopts a closed conformation. The SAXS analysis in solution clearly showed that IPMDH without a ligand adopts two distinct intermediate conformations, between the open and closed states, upon binding of NADH and IPM respectively, and adopts a fully closed conformation when in a ternary complex with NADH and IPM together.
AB - The structures of 3-isopropylmalate dehydrogenase (IPMDH) from Thermus thermophilus in complexes with its substrate, cofactor, and a cofactor analog were investigated by X-ray diffraction in a crystalline state and by small-angle X-ray scattering (SAXS) in solution. The structures at 2.8 Å resolution of the complexes with the substrate, 3-isopropylmalate (IPM), and with an analog of NAD, ADP-ribose, were both very close to the structure of the free enzyme, which adopts an open conformation. However, the binding of a ligand induced a small conformational change near the binding site. This result contrasts with results for NADP+-bound and isocitrate-bound isocitrate dehydrogenase (ICDH) from Escherichia coli, which adopts a closed conformation. The SAXS analysis in solution clearly showed that IPMDH without a ligand adopts two distinct intermediate conformations, between the open and closed states, upon binding of NADH and IPM respectively, and adopts a fully closed conformation when in a ternary complex with NADH and IPM together.
KW - 3-isopropylmalate dehydrogenase
KW - Conformation change
KW - E-S complex
KW - Thermus thermophilus
KW - X-ray crystallography
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U2 - 10.1093/oxfordjournals.jbchem.a124975
DO - 10.1093/oxfordjournals.jbchem.a124975
M3 - Article
C2 - 8576088
AN - SCOPUS:0028853604
VL - 118
SP - 745
EP - 752
JO - Journal of Biochemistry
JF - Journal of Biochemistry
SN - 0021-924X
IS - 4
ER -