4nr1

From Proteopedia

(Difference between revisions)

Revision as of 16:56, 21 January 2015

Structure of an oxygenase in complex with substrate

Structural highlights

4nr1 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
NonStd Res:
Related:	4jaa
Activity:	Hypoxia-inducible factor-asparagine dioxygenase, with EC number 1.14.11.30
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[HIF1N_HUMAN] Hydroxylates HIF-1 alpha at 'Asp-803' in the C-terminal transactivation domain (CAD). Functions as an oxygen sensor and, under normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300-interacting transactivator. Involved in transcriptional repression through interaction with HIF1A, VHL and histone deacetylases. Hydroxylates specific Asn residues within ankyrin repeat domains (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A and several other ARD-containing proteins. Also hydroxylates Asp and His residues within ARDs of ANK1 and TNKS2, respectively. Negatively regulates NOTCH1 activity, accelerating myogenic differentiation. Positively regulates ASB4 activity, promoting vascular differentiation.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8]

References

↑ Lando D, Peet DJ, Gorman JJ, Whelan DA, Whitelaw ML, Bruick RK. FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes Dev. 2002 Jun 15;16(12):1466-71. PMID:12080085 doi:10.1101/gad.991402
↑ Hewitson KS, McNeill LA, Riordan MV, Tian YM, Bullock AN, Welford RW, Elkins JM, Oldham NJ, Bhattacharya S, Gleadle JM, Ratcliffe PJ, Pugh CW, Schofield CJ. Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family. J Biol Chem. 2002 Jul 19;277(29):26351-5. Epub 2002 May 31. PMID:12042299 doi:10.1074/jbc.C200273200
↑ Cockman ME, Lancaster DE, Stolze IP, Hewitson KS, McDonough MA, Coleman ML, Coles CH, Yu X, Hay RT, Ley SC, Pugh CW, Oldham NJ, Masson N, Schofield CJ, Ratcliffe PJ. Posttranslational hydroxylation of ankyrin repeats in IkappaB proteins by the hypoxia-inducible factor (HIF) asparaginyl hydroxylase, factor inhibiting HIF (FIH). Proc Natl Acad Sci U S A. 2006 Oct 3;103(40):14767-72. Epub 2006 Sep 26. PMID:17003112
↑ Zheng X, Linke S, Dias JM, Zheng X, Gradin K, Wallis TP, Hamilton BR, Gustafsson M, Ruas JL, Wilkins S, Bilton RL, Brismar K, Whitelaw ML, Pereira T, Gorman JJ, Ericson J, Peet DJ, Lendahl U, Poellinger L. Interaction with factor inhibiting HIF-1 defines an additional mode of cross-coupling between the Notch and hypoxia signaling pathways. Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3368-73. doi:, 10.1073/pnas.0711591105. Epub 2008 Feb 25. PMID:18299578 doi:10.1073/pnas.0711591105
↑ Webb JD, Muranyi A, Pugh CW, Ratcliffe PJ, Coleman ML. MYPT1, the targeting subunit of smooth-muscle myosin phosphatase, is a substrate for the asparaginyl hydroxylase factor inhibiting hypoxia-inducible factor (FIH). Biochem J. 2009 May 13;420(2):327-33. doi: 10.1042/BJ20081905. PMID:19245366 doi:10.1042/BJ20081905
↑ Coleman ML, McDonough MA, Hewitson KS, Coles C, Mecinovic J, Edelmann M, Cook KM, Cockman ME, Lancaster DE, Kessler BM, Oldham NJ, Ratcliffe PJ, Schofield CJ. Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factor. J Biol Chem. 2007 Aug 17;282(33):24027-38. Epub 2007 Jun 15. PMID:17573339 doi:http://dx.doi.org/10.1074/jbc.M704102200
↑ Yang M, Chowdhury R, Ge W, Hamed RB, McDonough MA, Claridge TD, Kessler BM, Cockman ME, Ratcliffe PJ, Schofield CJ. Factor-Inhibiting Hypoxia-Inducible Factor (FIH) Catalyses the Posttranslational Hydroxylation of Histidinyl Residues within Ankyrin Repeat Domains. FEBS J. 2011 Jan 20. doi: 10.1111/j.1742-4658.2011.08022.x. PMID:21251231 doi:10.1111/j.1742-4658.2011.08022.x
↑ Yang M, Ge W, Chowdhury R, Claridge TD, Kramer HB, Schmierer B, McDonough MA, Gong L, Kessler BM, Ratcliffe PJ, Coleman ML, Schofield CJ. Asparagine and aspartate hydroxylation of the cytoskeletal ankyrin family is catalyzed by factor-inhibiting hypoxia-inducible factor. J Biol Chem. 2011 Mar 4;286(9):7648-60. Epub 2010 Dec 22. PMID:21177872 doi:10.1074/jbc.M110.193540

1 Structural highlights
2 Function
3 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4nr1"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+==Structure of an oxygenase in complex with substrate==
+<StructureSection load='4nr1' size='340' side='right' caption='[[4nr1]], [[Resolution|resolution]] 2.68&Aring;' scene=''>
-The entry 4nr1 is ON HOLD  until Paper Publication
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4nr1]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NR1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NR1 FirstGlance]. <br>
-Authors: Scotti, J.S., McDonough, M.A., Schofield, C.J.
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DYL:(2R)-2-AMINOPENT-4-ENOIC+ACID'>DYL</scene></td></tr>
-Description: Structure of an oxygenase in complex with substrate
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4jaa|4jaa]]</td></tr>
-[[Category: Unreleased Structures]]
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hypoxia-inducible_factor-asparagine_dioxygenase Hypoxia-inducible factor-asparagine dioxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.11.30 1.14.11.30] </span></td></tr>
-[[Category: Mcdonough, M.A]]
+<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=4nr1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nr1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4nr1 RCSB], [http://www.ebi.ac.uk/pdbsum/4nr1 PDBsum]</span></td></tr>
-[[Category: Scotti, J.S]]
+</table>
-[[Category: Schofield, C.J]]
+== Function ==
+[[http://www.uniprot.org/uniprot/HIF1N_HUMAN HIF1N_HUMAN]] Hydroxylates HIF-1 alpha at 'Asp-803' in the C-terminal transactivation domain (CAD). Functions as an oxygen sensor and, under normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300-interacting transactivator. Involved in transcriptional repression through interaction with HIF1A, VHL and histone deacetylases. Hydroxylates specific Asn residues within ankyrin repeat domains (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A and several other ARD-containing proteins. Also hydroxylates Asp and His residues within ARDs of ANK1 and TNKS2, respectively. Negatively regulates NOTCH1 activity, accelerating myogenic differentiation. Positively regulates ASB4 activity, promoting vascular differentiation.<ref>PMID:12080085</ref> <ref>PMID:12042299</ref> <ref>PMID:17003112</ref> <ref>PMID:18299578</ref> <ref>PMID:19245366</ref> <ref>PMID:17573339</ref> <ref>PMID:21251231</ref> <ref>PMID:21177872</ref>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Hypoxia-inducible factor-asparagine dioxygenase]]
+[[Category: McDonough, M A]]
+[[Category: Schofield, C J]]
+[[Category: Scotti, J S]]
+[[Category: 2-oxoglutarate]]
+[[Category: Activator-inhibitor]]
+[[Category: Ard]]
+[[Category: Asparaginyl/ aspartyl hydroxylase]]
+[[Category: Beta-hydroxylation]]
+[[Category: Dioxygenase]]
+[[Category: Dna-binding]]
+[[Category: Dsbh]]
+[[Category: Epigenetic regulation]]
+[[Category: Facial triad]]
+[[Category: Helix-loop-helix-beta]]
+[[Category: Iron]]
+[[Category: Metal-binding]]
+[[Category: On-heme]]
+[[Category: Oxidoreductase]]
+[[Category: Oxidoreductase-peptide complex]]
+[[Category: Oxygenase]]
+[[Category: Signaling]]
+[[Category: Transcription]]

4nr1

From Proteopedia

Revision as of 16:56, 21 January 2015

Structure of an oxygenase in complex with substrate

Structural highlights

Function

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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