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Factor-inhibiting hypoxia-inducible factor (FIH) catalyses the post-translational hydroxylation of histidinyl residues within ankyrin repeat domains

DOI: 10.1111/j.1742-4658.2011.08022.x DOI Help
PMID: 21251231 PMID Help

Authors: Ming Yang (University of Oxford) , Rasheduzzaman Chowdhury (University of Oxford) , Wei Ge (University of Oxford) , Refaat Hamed (University of Oxford) , Michael Mcdonough (University of Oxford) , Timothy Claridge (University of Oxford) , Benedikt Kessler (University of Oxford) , Matthew Cockman (University of Oxford) , Peter Ratcliffe (University of Oxford) , Christopher Schofield (University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Febs Letters , VOL 278 (7) , PAGES 1086-1097

State: Published (Approved)
Published: February 2011

Open Access Open Access

Abstract: Factor‐inhibiting hypoxia‐inducible factor (FIH) is an Fe(II)/2‐oxoglutarate‐dependent dioxygenase that acts as a negative regulator of the hypoxia‐inducible factor (HIF) by catalysing β‐hydroxylation of an asparaginyl residue in its C‐terminal transcriptional activation domain (CAD). In addition to the hypoxia‐inducible factor C‐terminal transcriptional activation domain (HIF‐CAD), FIH also catalyses asparaginyl hydroxylation of many ankyrin repeat domain‐containing proteins, revealing a broad sequence selectivity. However, there are few reports on the selectivity of FIH for the hydroxylation of specific residues. Here, we report that histidinyl residues within the ankyrin repeat domain of tankyrase‐2 can be hydroxylated by FIH. NMR and crystallographic analyses show that the histidinyl hydroxylation occurs at the β‐position. The results further expand the scope of FIH‐catalysed hydroxylations.

Journal Keywords: 2-oxoglutarate-dependent dioxygenase; ankyrin repeat domain;factor inhibiting HIF; histidinyl hydroxylation; post-translational hydroxylation

Subject Areas: Chemistry, Biology and Bio-materials

Instruments: I04-Macromolecular Crystallography

Added On: 06/04/2011 11:34

The FEBS Journal - 2011 - Yang - Factor%E2%80%90inhibiting hypoxia%E2%80%90inducible factor FIH catalyses the post%E2%80%90translational.pdf

Discipline Tags:

Biochemistry Chemistry Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)