6d0b: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older editNewer edit →
No edit summary
No edit summary
Line 1: Line 1:


==Crystal structure of PT1614 bound to HIF2a-B*:ARNT-B* complex==
==Crystal structure of PT1614 bound to HIF2a-B*:ARNT-B* complex==
<StructureSection load='6d0b' size='340' side='right' caption='[[6d0b]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
<StructureSection load='6d0b' size='340' side='right'caption='[[6d0b]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6d0b]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D0B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D0B FirstGlance]. <br>
<table><tr><td colspan='2'>[[6d0b]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D0B OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6D0B FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FOV:N-(3-chloro-5-fluorophenyl)-2-nitro-4-[(trifluoromethyl)sulfonyl]aniline'>FOV</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FOV:N-(3-chloro-5-fluorophenyl)-2-nitro-4-[(trifluoromethyl)sulfonyl]aniline'>FOV</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6czw|6czw]]</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6czw|6czw]]</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=6d0b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d0b OCA], [http://pdbe.org/6d0b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d0b RCSB], [http://www.ebi.ac.uk/pdbsum/6d0b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d0b ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6d0b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d0b OCA], [http://pdbe.org/6d0b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d0b RCSB], [http://www.ebi.ac.uk/pdbsum/6d0b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d0b ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
Line 16: Line 16:
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Du, X]]
[[Category: Du, X]]
[[Category: Arnt]]
[[Category: Arnt]]

Revision as of 12:02, 11 November 2020

Crystal structure of PT1614 bound to HIF2a-B*:ARNT-B* complexCrystal structure of PT1614 bound to HIF2a-B*:ARNT-B* complex

Structural highlights

6d0b is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[EPAS1_HUMAN] Defects in EPAS1 are the cause of familial erythrocytosis type 4 (ECYT4) [MIM:611783]. ECYT4 is an autosomal dominant disorder characterized by increased serum red blood cell mass, elevated hemoglobin concentration and hematocrit, and normal platelet and leukocyte counts.[1] [2] [3] [4]

Function

[EPAS1_HUMAN] Transcription factor involved in the induction of oxygen regulated genes. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Regulates the vascular endothelial growth factor (VEGF) expression and seems to be implicated in the development of blood vessels and the tubular system of lung. May also play a role in the formation of the endothelium that gives rise to the blood brain barrier. Potent activator of the Tie-2 tyrosine kinase expression. Activation seems to require recruitment of transcriptional coactivators such as CREBPB and probably EP300. Interaction with redox regulatory protein APEX seems to activate CTAD. [ARNT_HUMAN] Required for activity of the Ah (dioxin) receptor. This protein is required for the ligand-binding subunit to translocate from the cytosol to the nucleus after ligand binding. The complex then initiates transcription of genes involved in the activation of PAH procarcinogens. The heterodimer with HIF1A or EPAS1/HIF2A functions as a transcriptional regulator of the adaptive response to hypoxia.

References

  1. ↑ Furlow PW, Percy MJ, Sutherland S, Bierl C, McMullin MF, Master SR, Lappin TR, Lee FS. Erythrocytosis-associated HIF-2alpha mutations demonstrate a critical role for residues C-terminal to the hydroxylacceptor proline. J Biol Chem. 2009 Apr 3;284(14):9050-8. doi: 10.1074/jbc.M808737200. Epub 2009, Feb 10. PMID:19208626 doi:10.1074/jbc.M808737200
  2. ↑ Percy MJ, Beer PA, Campbell G, Dekker AW, Green AR, Oscier D, Rainey MG, van Wijk R, Wood M, Lappin TR, McMullin MF, Lee FS. Novel exon 12 mutations in the HIF2A gene associated with erythrocytosis. Blood. 2008 Jun 1;111(11):5400-2. doi: 10.1182/blood-2008-02-137703. Epub 2008, Mar 31. PMID:18378852 doi:10.1182/blood-2008-02-137703
  3. ↑ Percy MJ, Furlow PW, Lucas GS, Li X, Lappin TR, McMullin MF, Lee FS. A gain-of-function mutation in the HIF2A gene in familial erythrocytosis. N Engl J Med. 2008 Jan 10;358(2):162-8. doi: 10.1056/NEJMoa073123. PMID:18184961 doi:10.1056/NEJMoa073123
  4. ↑ Percy MJ, Chung YJ, Harrison C, Mercieca J, Hoffbrand AV, Dinardo CL, Santos PC, Fonseca GH, Gualandro SF, Pereira AC, Lappin TR, McMullin MF, Lee FS. Two new mutations in the HIF2A gene associated with erythrocytosis. Am J Hematol. 2012 Apr;87(4):439-42. doi: 10.1002/ajh.23123. Epub 2012 Feb 24. PMID:22367913 doi:10.1002/ajh.23123

6d0b, resolution 1.60Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=6d0b&oldid=3315718"