PDBsum entry 1sjs

Oxidoreductase

PDB id: 1sjs

Contents

Protein chain

415 a.a.

Waters ×90

References listed in PDB file

Key reference

• Title: Access to phosphorylation in isocitrate dehydrogenase may occur by domain shifting.
• Authors: J.Finer-Moore, S.E.Tsutakawa, D.R.Cherbavaz, D.C.Laporte, D.E.Koshland, R.M.Stroud.
• Ref.: Biochemistry, 1997, 36, 13890-13896. [DOI no: 10.1021/bi9711691]
• PubMed id: 9374867

Note In the PDB file this reference is annotated as "TO BE PUBLISHED". The citation details given above were identified by an automated search of PubMed on title and author names, giving a perfect match.

Abstract

To clarify further the mechanism of regulation by phosphorylation of isocitrate dehydrogenase, cocrystallization of isocitrate dehydrogenase and isocitrate dehydrogenase kinase/phosphatase in the presence of an ATP analog was attempted. Although cocrystallization was unsuccessful, a new crystal form of isocitrate dehydrogenase was obtained which provides insight into the phosphorylation mechanism. The new, orthorhombic crystal form of isocitrate dehydrogenase is related to the previously reported tetragonal form largely by an approximately 16 degrees shift of a large domain relative to the small domain and clasp region within each subunit of the dimeric enzyme. The NADP+ cofactor binding surface is significantly disrupted by the shift to the open conformation. The solvent-accessible surface area and surface-enclosed volume increase by 2% relative to the dimeric tetragonal form. Most of the increase results from expansion of the active site cleft such that the distance across its opening increases from approximately 5 to 13 A, significantly increasing accessibility to Ser-113. The conformation of isocitrate dehydrogenase in the orthorhombic crystal form more closely resembles that of the crystal structure of the homologous enzyme 3-isopropylmalate dehydrogenase than does the tetragonal isocitrate dehydrogenase conformation. Since the crystal lattice forces are fairly weak, it appears that isocitrate dehydrogenase is a flexible molecule that can easily undergo domain shifts and possibly other induced fit conformational changes, to accommodate binding to isocitrate dehydrogenase kinase/phosphatase.

Secondary reference #1

• Title: Regulation of isocitrate dehydrogenase by phosphorylation involves no long-Range conformational change in the free enzyme.
• Authors: J.H.Hurley, A.M.Dean, P.E.Thorsness, D.E.Koshland, R.M.Stroud.
• Ref.: J Biol Chem, 1990, 265, 3599-3602.
• PubMed id: 2406256

Secondary reference #2

• Title: Regulation of an enzyme by phosphorylation at the active site.
• Authors: J.H.Hurley, A.M.Dean, J.L.Sohl, D.E.Koshland, R.M.Stroud.
• Ref.: Science, 1990, 249, 1012-1016. [DOI no: 10.1126/science.2204109]
• PubMed id: 2204109

Secondary reference #3

• Title: Structure of a bacterial enzyme regulated by phosphorylation, Isocitrate dehydrogenase.
• Authors: J.H.Hurley, P.E.Thorsness, V.Ramalingam, N.H.Helmers, D.E.Koshland, R.M.Stroud.
• Ref.: Proc Natl Acad Sci U S A, 1989, 86, 8635-8639. [DOI no: 10.1073/pnas.86.22.8635]
• PubMed id: 2682654