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spinqualitylabelsall models PDB ID 1yci Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
, resolution 2.70Å
Ligands:	, and
Gene:	HIF1AN (Homo sapiens)
Activity:	Peptide-aspartate beta-dioxygenase, with EC number 1.14.11.16
Coordinates:	save as pdb, mmCIF, xml

Factor inhibiting HIF-1 alpha in complex with N-(carboxycarbonyl)-D-phenylalanine

Overview

A set of four non-heme iron(II) and 2-oxoglutarate-dependent enzymes catalyze the post-translational modification of a transcription factor, hypoxia inducible factor (HIF), that mediates the hypoxic response in animals. Hydroxylation of HIF both causes its degradation and limits its activity. We describe how the use of structural data coupled to solid-phase synthesis led to the discovery of a selective inhibitor of one of the HIF hydroxylases. The inhibitor N-oxalyl-d-phenylalanine was shown to inhibit the HIF asparaginyl hydroxylase (FIH) but not a HIF prolyl hydroxylase. A crystal structure of the inhibitor complexed to FIH reveals that it binds in the 2OG and, likely, in the dioxygen binding site. The results will help to enable the modulation of the hypoxic response for the up-regulation of specific genes of biomedical importance, such as erythropoietin and vascular endothelial growth factor.

About this Structure

1YCI is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Selective inhibition of factor inhibiting hypoxia-inducible factor., McDonough MA, McNeill LA, Tilliet M, Papamicael CA, Chen QY, Banerji B, Hewitson KS, Schofield CJ, J Am Chem Soc. 2005 Jun 1;127(21):7680-1. PMID:15913349

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