1yci
From Proteopedia
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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 with FE2, SO4 and NDF as ligands. Active as Peptide-aspartate beta-dioxygenase, with EC number 1.14.11.16 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
Page seeded by OCA on Mon Nov 12 20:17:53 2007
Categories: Homo sapiens | Peptide-aspartate beta-dioxygenase | Single protein | McDonough, M.A. | Schofield, C.J. | FE2 | NDF | SO4 | Asparaginyl hydroxylase | Dsbh | Fih | Hif | Hydroxylase n-(carboxycarbonyl)-d-phenylalanine | Hypoxia | Inhibitor 2-oxoglutarate | Ndf | Nofd | Oxygenase | Transcription
