2hbu: Difference between revisions
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{{STRUCTURE_2hbu| PDB=2hbu | SCENE= }} | {{STRUCTURE_2hbu| PDB=2hbu | SCENE= }} | ||
===Crystal structure of HIF prolyl hydroxylase EGLN-1 in complex with a biologically active inhibitor=== | |||
=== | ==Disease== | ||
[[http://www.uniprot.org/uniprot/EGLN1_HUMAN EGLN1_HUMAN]] Defects in EGLN1 are the cause of familial erythrocytosis type 3 (ECYT3) [MIM:[http://omim.org/entry/609820 609820]]. ECYT3 is an autosomal dominant disorder characterized by increased serum red blood cell mass, elevated serum hemoglobin and hematocrit, and normal serum erythropoietin levels.<ref>PMID:16407130</ref><ref>PMID:17579185</ref> | |||
==Function== | |||
[[http://www.uniprot.org/uniprot/EGLN1_HUMAN EGLN1_HUMAN]] Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF1B. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN1 is the most important isozyme under normoxia and, through regulating the stability of HIF1, involved in various hypoxia-influenced processes such as angiogenesis in retinal and cardiac functionality.<ref>PMID:11595184</ref><ref>PMID:12351678</ref><ref>PMID:15897452</ref><ref>PMID:19339211</ref><ref>PMID:21792862</ref> | |||
==About this Structure== | ==About this Structure== | ||
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*[[Hypoxia-inducible factor prolyl hydroxylase|Hypoxia-inducible factor prolyl hydroxylase]] | *[[Hypoxia-inducible factor prolyl hydroxylase|Hypoxia-inducible factor prolyl hydroxylase]] | ||
*[[Prolyl hydroxylase domain|Prolyl hydroxylase domain]] | *[[Prolyl hydroxylase domain|Prolyl hydroxylase domain]] | ||
==Reference== | |||
<references group="xtra"/><references/> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Boyer, A.]] | [[Category: Boyer, A.]] | ||
