4kbz

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
==Crystal Structure of Hypoxia-Inducible Factor Prolyl Hydroxylase (PHD2) with (S)-{2-[2-(5-Cyano-3-hydroxy-pyridin-2-yl)-thiazol-4-yl]-acetylamino}-phenyl-acetic acid==
==Crystal Structure of Hypoxia-Inducible Factor Prolyl Hydroxylase (PHD2) with (S)-{2-[2-(5-Cyano-3-hydroxy-pyridin-2-yl)-thiazol-4-yl]-acetylamino}-phenyl-acetic acid==
-
<StructureSection load='4kbz' size='340' side='right' caption='[[4kbz]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
+
<StructureSection load='4kbz' size='340' side='right'caption='[[4kbz]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[4kbz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KBZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KBZ FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[4kbz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KBZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KBZ FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1QA:(2S)-({[2-(5-CYANO-3-HYDROXYPYRIDIN-2-YL)-1,3-THIAZOL-4-YL]ACETYL}AMINO)(PHENYL)ETHANOIC+ACID'>1QA</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1QA:(2S)-({[2-(5-CYANO-3-HYDROXYPYRIDIN-2-YL)-1,3-THIAZOL-4-YL]ACETYL}AMINO)(PHENYL)ETHANOIC+ACID'>1QA</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2hbu|2hbu]], [[2g19|2g19]], [[2g1m|2g1m]]</td></tr>
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4kbz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kbz OCA], [https://pdbe.org/4kbz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kbz RCSB], [https://www.ebi.ac.uk/pdbsum/4kbz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kbz ProSAT]</span></td></tr>
-
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EGLN1, C1orf12, PNAS-118, PNAS-137 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+
-
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hypoxia-inducible_factor-proline_dioxygenase Hypoxia-inducible factor-proline dioxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.11.29 1.14.11.29] </span></td></tr>
+
-
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4kbz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kbz OCA], [http://pdbe.org/4kbz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kbz RCSB], [http://www.ebi.ac.uk/pdbsum/4kbz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kbz ProSAT]</span></td></tr>
+
</table>
</table>
== Disease ==
== 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>
+
[https://www.uniprot.org/uniprot/EGLN1_HUMAN EGLN1_HUMAN] Defects in EGLN1 are the cause of familial erythrocytosis type 3 (ECYT3) [MIM:[https://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 ==
== 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>
+
[https://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>
 +
 
 +
==See Also==
 +
*[[Prolyl hydroxylase domain|Prolyl hydroxylase domain]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
-
[[Category: Human]]
+
[[Category: Homo sapiens]]
-
[[Category: Hypoxia-inducible factor-proline dioxygenase]]
+
[[Category: Large Structures]]
-
[[Category: Chang, H J]]
+
[[Category: Chang HJ]]
-
[[Category: Hong, Y R]]
+
[[Category: Hong YR]]
-
[[Category: Kim, H T]]
+
[[Category: Kim HT]]
-
[[Category: Hif]]
+
-
[[Category: Jelly-roll beta-strand core]]
+
-
[[Category: Oxidoreductase]]
+

Revision as of 11:51, 30 November 2022

Crystal Structure of Hypoxia-Inducible Factor Prolyl Hydroxylase (PHD2) with (S)-{2-[2-(5-Cyano-3-hydroxy-pyridin-2-yl)-thiazol-4-yl]-acetylamino}-phenyl-acetic acid

PDB ID 4kbz

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4kbz"
Personal tools