1h2n | pdb_00001h2n

FACTOR INHIBITING HIF-1 ALPHA

spinqualitylabelsall models 1h2n, resolution 2.84Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1h2n is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: AKG, FE2, SO4 Related: 1h2k, 1h2l, 1h2m Activity: Peptide-aspartate beta-dioxygenase, with EC number 1.14.11.16 Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The activity of the transcription factor hypoxia-inducible factor (HIF) is regulated by oxygen-dependent hydroxylation. Under normoxic conditions, hydroxylation of proline residues triggers destruction of its alpha-subunit while hydroxylation of Asn(803) in the C-terminal transactivation domain of HIF-1 alpha (CAD) prevents its interaction with p300. Here we report crystal structures of the asparagine hydroxylase (factor-inhibiting HIF, FIH) complexed with Fe((II)), 2-oxoglutarate cosubstrate, and CAD fragments, which reveal the structural basis of HIF modification. CAD binding to FIH occurs via an induced fit process at two distinct interaction sites. At the hydroxylation site CAD adopts a loop conformation, contrasting with a helical conformation for the same residues when bound to p300. Asn(803) of CAD is buried and precisely orientated in the active site such that hydroxylation occurs at its beta-carbon. Together with structures with the inhibitors Zn((II)) and N-oxaloylglycine, analysis of the FIH-CAD complexes will assist design of hydroxylase inhibitors with proangiogenic properties. Conserved structural motifs within FIH imply it is one of an extended family of Fe((II)) oxygenases involved in gene regulation. Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alpha.,Elkins JM, Hewitson KS, McNeill LA, Seibel JF, Schlemminger I, Pugh CW, Ratcliffe PJ, Schofield CJ J Biol Chem. 2003 Jan 17;278(3):1802-6. Epub 2002 Nov 21. PMID:12446723 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Factor inhibiting HIF

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