1sjs
From Proteopedia
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ACCESS TO PHOSPHORYLATION IN ISOCITRATE DEHYDROGENASE MAY OCCUR BY DOMAIN SHIFTING
Overview
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.
About this Structure
1SJS is a Single protein structure of sequence from Escherichia coli. Active as Isocitrate dehydrogenase (NADP(+)), with EC number 1.1.1.42 Structure known Active Site: POS. Full crystallographic information is available from OCA.
Reference
Access to phosphorylation in isocitrate dehydrogenase may occur by domain shifting., Finer-Moore J, Tsutakawa SE, Cherbavaz DR, LaPorte DC, Koshland DE Jr, Stroud RM, Biochemistry. 1997 Nov 11;36(45):13890-6. PMID:9374867
Page seeded by OCA on Mon Nov 5 17:04:33 2007
