Evidence that two enzyme-derived histidine ligands are sufficient for iron binding and catalysis by factor inhibiting HIF (FIH).

Journal article

A 2-His-1-carboxylate triad of iron binding residues is present in many non-heme iron oxygenases including the Fe(II) and 2-oxoglutarate (2OG)-dependent dioxygenases. Three variants (D201A, D201E, and D201G) of the iron binding Asp-201 residue of an asparaginyl hydroxylase, factor inhibiting HIF (FIH), were made and analyzed. FIH-D201A and FIH-D201E did not catalyze asparaginyl hydroxylation, but in the presence of a reducing agent, they displayed enhanced 2OG turnover when compared with wild...

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Authors: Hewitson, K; Holmes, S; Ehrismann, D; Hardy, A; Chowdhury, R

• Publication status: Published
• Journal: Journal of biological chemistry
• Volume: 283
• Issue: 38
• Pages: 25971-25978
• Publication date: 2008-09-01
• DOI: 10.1074/jbc.m804999200
• EISSN: 1083-351X
• ISSN: 0021-9258
• Language: English
• Keywords: Metals; Humans; Heme; Crystallography, X-Ray; Iron; Dioxygenases; Ketoglutaric Acids; Protein Binding; Repressor Proteins; Ligands; Models, Chemical; Histidine; Mixed Function Oxygenases; Catalysis; Models, Molecular; Molecular Conformation