1mze: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
|PDB= 1mze |SIZE=350|CAPTION= <scene name='initialview01'>1mze</scene>, resolution 2.20Å | |PDB= 1mze |SIZE=350|CAPTION= <scene name='initialview01'>1mze</scene>, resolution 2.20Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand= | |LIGAND= <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=TAR:D(-)-TARTARIC+ACID'>TAR</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= FIH-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= FIH-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1mzf|1MZF]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1mze FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mze OCA], [http://www.ebi.ac.uk/pdbsum/1mze PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1mze RCSB]</span> | |||
}} | }} | ||
| Line 25: | Line 28: | ||
[[Category: Deisenhofer, J.]] | [[Category: Deisenhofer, J.]] | ||
[[Category: III, C E.Dann.]] | [[Category: III, C E.Dann.]] | ||
[[Category: beta-jellyroll]] | [[Category: beta-jellyroll]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:23:11 2008'' | ||
Revision as of 22:23, 30 March 2008
| |||||||
| , resolution 2.20Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | FIH-1 (Homo sapiens) | ||||||
| Related: | 1MZF
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human Factor Inhibiting HIF (FIH1)
OverviewOverview
Precise regulation of the evolutionarily conserved hypoxia-inducible transcription factor (HIF) ensures proper adaptation to variations in oxygen availability throughout development and into adulthood. Oxygen-dependent regulation of HIF stability and activity are mediated by hydroxylation of conserved proline and asparagine residues, respectively. Because the relevant prolyl and asparginyl hydroxylases use O(2) to effect these posttranslational modifications, these enzymes are implicated as direct oxygen sensors in the mammalian hypoxic response pathway. Here we present the structure of factor-inhibiting HIF-1 (FIH-1), the pertinent asparaginyl hydroxylase involved in hypoxic signaling. Hydroxylation of the C-terminal transactivation domain (CTAD) of HIF by FIH-1 prevents CTAD association with transcriptional coactivators under normoxic conditions. Consistent with other structurally known hydroxylases, FIH-1 is comprised of a beta-strand jellyroll core with both Fe(II) and the cosubstrate 2-oxoglutarate bound in the active site. Details of the molecular contacts at the active site of FIH-1 have been elucidated and provide a platform for future drug design. Furthermore, the structure reveals the presence of a FIH-1 homodimer that forms in solution and is essential for FIH activity.
About this StructureAbout this Structure
1MZE is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structure of factor-inhibiting hypoxia-inducible factor 1: An asparaginyl hydroxylase involved in the hypoxic response pathway., Dann CE 3rd, Bruick RK, Deisenhofer J, Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15351-6. Epub 2002 Nov 13. PMID:12432100
Page seeded by OCA on Sun Mar 30 22:23:11 2008