1xk0: Difference between revisions
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
<StructureSection load='1xk0' size='340' side='right'caption='[[1xk0]], [[Resolution|resolution]] 2.18Å' scene=''> | <StructureSection load='1xk0' size='340' side='right'caption='[[1xk0]], [[Resolution|resolution]] 2.18Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1xk0]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[1xk0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XK0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XK0 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NO:NITRIC+OXIDE'>NO</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NO:NITRIC+OXIDE'>NO</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1xjz|1xjz]], [[1xk1|1xk1]], [[1xk2|1xk2]], [[1xk3|1xk3]]</div></td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1xjz|1xjz]], [[1xk1|1xk1]], [[1xk2|1xk2]], [[1xk3|1xk3]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HMOX1, HO1, HO ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HMOX1, HO1, HO ([https://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'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Heme_oxygenase Heme oxygenase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.3 1.14.99.3] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1xk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xk0 OCA], [https://pdbe.org/1xk0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xk0 RCSB], [https://www.ebi.ac.uk/pdbsum/1xk0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xk0 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
[[ | [[https://www.uniprot.org/uniprot/HMOX1_HUMAN HMOX1_HUMAN]] Defects in HMOX1 are the cause of heme oxygenase 1 deficiency (HMOX1D) [MIM:[https://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> | ||
== Function == | == Function == | ||
[[ | [[https://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. | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Revision as of 19:41, 20 October 2021
Crystal Structures of the G139A, G139A-NO and G143H Mutants of Human Heme Oxygenase-1Crystal Structures of the G139A, G139A-NO and G143H Mutants of Human Heme Oxygenase-1
Structural highlights
Disease[HMOX1_HUMAN] Defects in HMOX1 are the cause of heme oxygenase 1 deficiency (HMOX1D) [MIM: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.[1] Function[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. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedConserved glycines, Gly139 and Gly143, in the distal helix of human heme oxygenase-1 (HO-1) provide the flexibility required for the opening and closing of the heme active site for substrate binding and product dissociation during HO-1 catalysis. Earlier mutagenesis work on human HO-1 showed that replacement of either Gly139 or Gly143 suppresses heme oxygenase activity and, in the case of the Gly139 mutants, increases peroxidase activity (Liu et al. in J. Biol. Chem. 275:34501, 2000). To further investigate the role of the conserved distal helix glycines, we have determined the crystal structures of the human HO-1 G139A mutant, the G139A mutant in a complex with NO, and the G143H mutant at 1.88, 2.18 and 2.08 A, respectively. The results confirm that fine tuning of the previously noted active-site hydrogen-bonding network is critical in determining whether heme oxygenase or peroxidase activity is observed. Crystal structures of the G139A, G139A-NO and G143H mutants of human heme oxygenase-1. A finely tuned hydrogen-bonding network controls oxygenase versus peroxidase activity.,Lad L, Koshkin A, de Montellano PR, Poulos TL J Biol Inorg Chem. 2005 Mar;10(2):138-46. Epub 2005 Feb 3. PMID:15690204[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||||||