2cgo

File:2cgo.gif

spinqualitylabelsall models 2cgo, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

FACTOR INHIBITING HIF-1 ALPHA WITH FUMARATE

OverviewOverview

In humans both the levels and activity of the alpha-subunit of the, hypoxia-inducible transcription factor (HIF-alpha) are regulated by its, post-translation hydroxylation as catalyzed by iron- and 2-oxoglutarate, (2OG)-dependent prolyl and asparaginyl hydroxylases (PHD1-3 and, factor-inhibiting HIF (FIH), respectively). One consequence of hypoxia is, the accumulation of tricarboxylic acid cycle intermediates (TCAIs). In, vitro assays were used to assess non-2OG TCAIs as inhibitors of purified, PHD2 and FIH. Under the assay conditions, no significant FIH inhibition, was observed by the TCAIs or pyruvate, but fumarate, succinate, and, isocitrate inhibited PHD2. Mass spectrometric analyses under nondenaturing, conditions were used to investigate the binding of TCAIs to PHD2 and, supported ... [(full description)]

About this StructureAbout this Structure

2CGO is a [Single protein] structure of sequence from [Homo sapiens] with FE, SO4 and FMR as [ligands]. Active as [Peptide-aspartate beta-dioxygenase], with EC number [1.14.11.16]. Structure known Active Site: AC1. Full crystallographic information is available from [OCA].

ReferenceReference

Structural and mechanistic studies on the inhibition of the hypoxia-inducible transcription factor hydroxylases by tricarboxylic acid cycle intermediates., Hewitson KS, Lienard BM, McDonough MA, Clifton IJ, Butler D, Soares AS, Oldham NJ, McNeill LA, Schofield CJ, J Biol Chem. 2007 Feb 2;282(5):3293-301. Epub 2006 Nov 29. PMID:17135241

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