2y34

From Proteopedia

(Difference between revisions)

Revision as of 08:03, 4 November 2020

S-nitrosylated PHD2 (NO exposed) in complex with Fe(II) and UN9

Structural highlights

2y34 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Related:	2hbt, 2g1m, 2g19, 2hbu, 2y33
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[EGLN1_HUMAN] Defects in EGLN1 are the cause of familial erythrocytosis type 3 (ECYT3) [MIM: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.^[1] ^[2]

Function

[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.^[3] ^[4] ^[5] ^[6] ^[7]

Publication Abstract from PubMed

The hypoxic response in animals is mediated via the transcription factor hypoxia-inducible factor (HIF). An oxygen-sensing component of the HIF system is provided by Fe(II) and 2-oxoglutarate-dependent oxygenases that catalyse the posttranslational hydroxylation of the HIF-alpha subunit. It is proposed that the activity of the HIF hydroxylases can be regulated by their reaction with nitric oxide. We describe biochemical and biophysical studies on the reaction of prolyl hydroxylase domain-containing enzyme (PHD) isoform 2 (EGLN1) with nitric oxide and a nitric oxide transfer reagent. The combined results reveal the potential for the catalytic domain of PHD2 to react with nitric oxide both at its Fe(II) and at cysteine residues. Although the biological significance is unclear, the results suggest that the reaction of PHD2 with nitric oxide has the potential to be complex and are consistent with proposals based on cellular studies that nitric oxide may regulate the hypoxic response by direct reaction with the HIF hydroxylases.

Studies on the Reaction of Nitric Oxide with the Hypoxia-Inducible Factor Prolyl Hydroxylase Domain 2 (EGLN1).,Chowdhury R, Flashman E, Mecinovic J, Kramer HB, Kessler BM, Frapart YM, Boucher JL, Clifton IJ, McDonough MA, Schofield CJ J Mol Biol. 2011 Jul 8;410(2):268-79. Epub 2011 May 13. PMID:21601578^[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Percy MJ, Zhao Q, Flores A, Harrison C, Lappin TR, Maxwell PH, McMullin MF, Lee FS. A family with erythrocytosis establishes a role for prolyl hydroxylase domain protein 2 in oxygen homeostasis. Proc Natl Acad Sci U S A. 2006 Jan 17;103(3):654-9. Epub 2006 Jan 9. PMID:16407130 doi:0508423103
↑ Percy MJ, Furlow PW, Beer PA, Lappin TR, McMullin MF, Lee FS. A novel erythrocytosis-associated PHD2 mutation suggests the location of a HIF binding groove. Blood. 2007 Sep 15;110(6):2193-6. Epub 2007 Jun 19. PMID:17579185 doi:10.1182/blood-2007-04-084434
↑ Epstein AC, Gleadle JM, McNeill LA, Hewitson KS, O'Rourke J, Mole DR, Mukherji M, Metzen E, Wilson MI, Dhanda A, Tian YM, Masson N, Hamilton DL, Jaakkola P, Barstead R, Hodgkin J, Maxwell PH, Pugh CW, Schofield CJ, Ratcliffe PJ. C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell. 2001 Oct 5;107(1):43-54. PMID:11595184
↑ Ivan M, Haberberger T, Gervasi DC, Michelson KS, Gunzler V, Kondo K, Yang H, Sorokina I, Conaway RC, Conaway JW, Kaelin WG Jr. Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor. Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13459-64. Epub 2002 Sep 26. PMID:12351678 doi:10.1073/pnas.192342099
↑ Ozer A, Wu LC, Bruick RK. The candidate tumor suppressor ING4 represses activation of the hypoxia inducible factor (HIF). Proc Natl Acad Sci U S A. 2005 May 24;102(21):7481-6. Epub 2005 May 16. PMID:15897452 doi:0502716102
↑ Yasumoto K, Kowata Y, Yoshida A, Torii S, Sogawa K. Role of the intracellular localization of HIF-prolyl hydroxylases. Biochim Biophys Acta. 2009 May;1793(5):792-7. doi: 10.1016/j.bbamcr.2009.01.014. , Epub 2009 Feb 5. PMID:19339211 doi:10.1016/j.bbamcr.2009.01.014
↑ Su Y, Loos M, Giese N, Metzen E, Buchler MW, Friess H, Kornberg A, Buchler P. Prolyl hydroxylase-2 (PHD2) exerts tumor-suppressive activity in pancreatic cancer. Cancer. 2012 Feb 15;118(4):960-72. doi: 10.1002/cncr.26344. Epub 2011 Jul 26. PMID:21792862 doi:10.1002/cncr.26344
↑ Chowdhury R, Flashman E, Mecinovic J, Kramer HB, Kessler BM, Frapart YM, Boucher JL, Clifton IJ, McDonough MA, Schofield CJ. Studies on the Reaction of Nitric Oxide with the Hypoxia-Inducible Factor Prolyl Hydroxylase Domain 2 (EGLN1). J Mol Biol. 2011 Jul 8;410(2):268-79. Epub 2011 May 13. PMID:21601578 doi:10.1016/j.jmb.2011.04.075

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2y34"

@@ Line 1: / Line 1: @@
 ==S-nitrosylated PHD2 (NO exposed) in complex with Fe(II) and UN9==
-<StructureSection load='2y34' size='340' side='right' caption='[[2y34]], [[Resolution|resolution]] 2.01&Aring;' scene=''>
+<StructureSection load='2y34' size='340' side='right'caption='[[2y34]], [[Resolution|resolution]] 2.01&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2y34]] 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=2Y34 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Y34 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2y34]] 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=2Y34 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2Y34 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=UN9:N-[(1-CHLORO-4-HYDROXYISOQUINOLIN-3-YL)CARBONYL]GLYCINE'>UN9</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=UN9:N-[(1-CHLORO-4-HYDROXYISOQUINOLIN-3-YL)CARBONYL]GLYCINE'>UN9</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SNC:S-NITROSO-CYSTEINE'>SNC</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2hbt|2hbt]], [[2g1m|2g1m]], [[2g19|2g19]], [[2hbu|2hbu]], [[2y33|2y33]]</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=2y34 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y34 OCA], [http://pdbe.org/2y34 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2y34 RCSB], [http://www.ebi.ac.uk/pdbsum/2y34 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2y34 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=2y34 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y34 OCA], [http://pdbe.org/2y34 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2y34 RCSB], [http://www.ebi.ac.uk/pdbsum/2y34 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2y34 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 30: / Line 30: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Chowdhury, R]]
 [[Category: McDonough, M A]]

2y34

From Proteopedia

Revision as of 08:03, 4 November 2020

S-nitrosylated PHD2 (NO exposed) in complex with Fe(II) and UN9

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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