1iz3
From Proteopedia
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'''Dimeric structure of FIH (Factor inhibiting HIF)''' | '''Dimeric structure of FIH (Factor inhibiting HIF)''' | ||
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[[Category: Lee, S M.]] | [[Category: Lee, S M.]] | ||
[[Category: Ryu, S E.]] | [[Category: Ryu, S E.]] | ||
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| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 20:36:29 2008'' | |
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Revision as of 17:36, 2 May 2008
Dimeric structure of FIH (Factor inhibiting HIF)
Overview
The master switch of cellular hypoxia responses, hypoxia-inducible factor 1 (HIF-1), is hydroxylated by factor inhibiting HIF-1 (FIH-1) at a conserved asparagine residue under normoxia, which suppresses transcriptional activity of HIF-1 by abrogating its interaction with transcription coactivators. Here we report the crystal structure of human FIH-1 at 2.8-A resolution. The structural core of FIH-1 consists of a jellyroll-like beta-barrel containing the conserved ferrous-binding triad residues, confirming that FIH-1 is a member of the 2-oxoglutarate-dependent dioxygenase family. Except for the core structure and triad residues, FIH-1 has many structural deviations from other family members including N- and C-terminal insertions and various deletions in the middle of the structure. The ferrous-binding triad region is highly exposed to the solvent, which is connected to a prominent groove that may bind to a helix near the hydroxylation site of HIF-1. The structure, which is in a dimeric state, also reveals the putative von Hippel-Lindau-binding site that is distinctive to the putative HIF-1-binding site, supporting the formation of the ternary complex by FIH-1, HIF-1, and von Hippel-Lindau. The unique environment of the active site and cofactor-binding region revealed in the structure should allow design of selective drugs that can be used in ischemic diseases to promote hypoxia responses.
About this Structure
1IZ3 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of human FIH-1 reveals a unique active site pocket and interaction sites for HIF-1 and von Hippel-Lindau., Lee C, Kim SJ, Jeong DG, Lee SM, Ryu SE, J Biol Chem. 2003 Feb 28;278(9):7558-63. Epub 2002 Dec 12. PMID:12482756 Page seeded by OCA on Fri May 2 20:36:29 2008
