3hok

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{{STRUCTURE_3hok| PDB=3hok | SCENE= }}
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==X-ray Crystal Structure of Human Heme Oxygenase-1 with (2R, 4S)-2-[2-(4-Chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4[((5-trifluoromethylpyridin-2-yl)thio)methyl]-1,3-dioxolane: A Novel, Inducible Binding Mode==
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===X-ray Crystal Structure of Human Heme Oxygenase-1 with (2R, 4S)-2-[2-(4-Chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4[((5-trifluoromethylpyridin-2-yl)thio)methyl]-1,3-dioxolane: A Novel, Inducible Binding Mode===
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<StructureSection load='3hok' size='340' side='right' caption='[[3hok]], [[Resolution|resolution]] 2.19&Aring;' scene=''>
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{{ABSTRACT_PUBMED_19601578}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3hok]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HOK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HOK FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=Q80:2-({[(2R,4S)-2-[2-(4-CHLOROPHENYL)ETHYL]-2-(1H-IMIDAZOL-1-YLMETHYL)-1,3-DIOXOLAN-4-YL]METHYL}SULFANYL)-5-(TRIFLUOROMETHYL)PYRIDINE'>Q80</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3czy|3czy]], [[1n45|1n45]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HMOX1, HO, HO1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Heme_oxygenase Heme oxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.3 1.14.99.3] </span></td></tr>
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<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=3hok FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hok OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hok RCSB], [http://www.ebi.ac.uk/pdbsum/3hok PDBsum]</span></td></tr>
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</table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/HMOX1_HUMAN HMOX1_HUMAN]] Defects in HMOX1 are the cause of heme oxygenase 1 deficiency (HMOX1D) [MIM:[http://omim.org/entry/614034 614034]]. A disease characterized by impaired stress hematopoiesis, resulting in marked erythrocyte fragmentation and intravascular hemolysis, coagulation abnormalities, endothelial damage, and iron deposition in renal and hepatic tissues. Clinical features include persistent hemolytic anemia, asplenia, nephritis, generalized erythematous rash, growth retardation and hepatomegaly.<ref>PMID:9884342</ref>
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== Function ==
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[[http://www.uniprot.org/uniprot/HMOX1_HUMAN HMOX1_HUMAN]] Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the activity of heme oxygenase is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ho/3hok_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The crystal structure of human heme oxygenase-1 (HO-1) in complex with (2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4[((5-tri fluoromethylpyridin-2-yl)thio)methyl]-1,3-dioxolane (4) reveals a novel, inducible binding mode. Inhibitor 4 coordinates the heme iron, with its chlorophenyl group bound in a distal hydrophobic pocket, as seen in previous structures. However, accommodation of the 5-trifluoromethylpyridin-2-yl group requires a significant shift in the proximal helix, inducing the formation of a hydrophobic pocket. This is the first example of an induced binding pocket observed in HO-1.
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==Disease==
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X-ray Crystal Structure of Human Heme Oxygenase-1 with (2R,4S)-2-[2-(4-Chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4[((5-tri fluoromethylpyridin-2-yl)thio)methyl]-1,3-dioxolane: A Novel, Inducible Binding Mode.,Rahman MN, Vlahakis JZ, Vukomanovic D, Szarek WA, Nakatsu K, Jia Z J Med Chem. 2009 Jul 14. PMID:19601578<ref>PMID:19601578</ref>
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[[http://www.uniprot.org/uniprot/HMOX1_HUMAN HMOX1_HUMAN]] Defects in HMOX1 are the cause of heme oxygenase 1 deficiency (HMOX1D) [MIM:[http://omim.org/entry/614034 614034]]. A disease characterized by impaired stress hematopoiesis, resulting in marked erythrocyte fragmentation and intravascular hemolysis, coagulation abnormalities, endothelial damage, and iron deposition in renal and hepatic tissues. Clinical features include persistent hemolytic anemia, asplenia, nephritis, generalized erythematous rash, growth retardation and hepatomegaly.<ref>PMID:9884342</ref>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[http://www.uniprot.org/uniprot/HMOX1_HUMAN HMOX1_HUMAN]] Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the activity of heme oxygenase is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed.
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</div>
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==About this Structure==
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[[3hok]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HOK OCA].
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==See Also==
==See Also==
*[[Heme oxygenase|Heme oxygenase]]
*[[Heme oxygenase|Heme oxygenase]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:019601578</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Heme oxygenase]]
[[Category: Heme oxygenase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Jia, Z.]]
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[[Category: Jia, Z]]
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[[Category: Rahman, M N.]]
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[[Category: Rahman, M N]]
[[Category: Alpha helice]]
[[Category: Alpha helice]]
[[Category: Endoplasmic reticulum]]
[[Category: Endoplasmic reticulum]]

Revision as of 16:29, 18 December 2014

X-ray Crystal Structure of Human Heme Oxygenase-1 with (2R, 4S)-2-[2-(4-Chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4[((5-trifluoromethylpyridin-2-yl)thio)methyl]-1,3-dioxolane: A Novel, Inducible Binding Mode

3hok, resolution 2.19Å

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