2Y0I

FACTOR INHIBITING HIF-1 ALPHA IN COMPLEX WITH TANKYRASE-2 (TNKS2) FRAGMENT PEPTIDE (21-MER)

Summary for 2Y0I

• Entry DOI: 10.2210/pdb2y0i/pdb
• Related: 1H2K 1H2L 1H2M 1H2N 1IZ3 1MZE 1MZF 1YCI 2CGN 2CGO 2W0X 2WA3 2WA4 2XUM
• Descriptor: HYPOXIA-INDUCIBLE FACTOR 1-ALPHA INHIBITOR, TANKYRASE-2, FE (II) ION, ... (7 entities in total)
• Functional Keywords: oxidoreductase-peptide complex, dioxygenase, helix-loop-helix-beta, facial triad, asparaginyl/aspartyl hydroxylase, ankyrin repeat domain, oxidoreductase/peptide
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Nucleus: Q9NWT6; Cytoplasm: Q9H2K2
• Total number of polymer chains: 2
• Total formula weight: 43611.50

Authors

Chowdhury, R.,McDonough, M.A.,Schofield, C.J. (deposition date: 2010-12-02, release date: 2011-02-02, Last modification date: 2023-12-20)

Primary citation

Yang, M.,Chowdhury, R.,Ge, W.,Hamed, R.B.,McDonough, M.A.,Claridge, T.D.,Kessler, B.M.,Cockman, M.E.,Ratcliffe, P.J.,Schofield, C.J.
Factor-inhibiting hypoxia-inducible factor (FIH) catalyses the post-translational hydroxylation of histidinyl residues within ankyrin repeat domains.
FEBS J., 278:1086-1097, 2011

PubMed 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.

PubMed: 21251231
DOI: 10.1111/j.1742-4658.2011.08022.x

Experimental method

X-RAY DIFFRACTION (2.28 Å)