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ID: ALA1255189

Journal: Bioorg Med Chem Lett

Title: Structural basis for binding of cyclic 2-oxoglutarate analogues to factor-inhibiting hypoxia-inducible factor.

Authors: Conejo-Garcia A, McDonough MA, Loenarz C, McNeill LA, Hewitson KS, Ge W, Liénard BM, Schofield CJ, Clifton IJ.

Abstract: Aromatic analogues of the 2-oxoglutarate co-substrate of the hypoxia-inducible factor hydroxylases are shown to bind at the active site iron: Pyridine-2,4-dicarboxylate binds as anticipated with a single molecule chelating the iron in a bidentate manner. The binding mode of a hydroxamic acid analogue, at least in the crystalline state, is unusual because two molecules of the inhibitor are observed at the active site and partial displacement of the iron binding aspartyl residue was observed.

CiteXplore: 20822901

DOI: 10.1016/j.bmcl.2010.08.032