Ligand-induced changes in the conformation of 3-isopropylmalate dehydrogenase from Thermus thermophilus

Shojiro Kadono, Masahiro Sakurai, Hideaki Moriyama, Mamoru Sato, Yoko Hayashi, Tairo Oshima, Nobuo Tanaka

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)745-752
Number of pages8
JournalJournal of Biochemistry
Volume118
Issue number4
DOIs
StatePublished - Jan 1 1995

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3-Isopropylmalate Dehydrogenase
Thermus thermophilus
NAD
Conformations
Ligands
X ray scattering
X-Rays
Adenosine Diphosphate Ribose
Isocitrate Dehydrogenase
NADP
X-Ray Diffraction
Oxidoreductases
Substrates
Binding Sites
Escherichia coli
Enzymes
Crystalline materials
X ray diffraction

Keywords

  • 3-isopropylmalate dehydrogenase
  • Conformation change
  • E-S complex
  • Thermus thermophilus
  • X-ray crystallography

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Ligand-induced changes in the conformation of 3-isopropylmalate dehydrogenase from Thermus thermophilus. / Kadono, Shojiro; Sakurai, Masahiro; Moriyama, Hideaki; Sato, Mamoru; Hayashi, Yoko; Oshima, Tairo; Tanaka, Nobuo.

In: Journal of Biochemistry, Vol. 118, No. 4, 01.01.1995, p. 745-752.

Research output: Contribution to journalArticle

Kadono, Shojiro ; Sakurai, Masahiro ; Moriyama, Hideaki ; Sato, Mamoru ; Hayashi, Yoko ; Oshima, Tairo ; Tanaka, Nobuo. / Ligand-induced changes in the conformation of 3-isopropylmalate dehydrogenase from Thermus thermophilus. In: Journal of Biochemistry. 1995 ; Vol. 118, No. 4. pp. 745-752.
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