1xk0: Difference between revisions
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caption="1xk0, resolution 2.18Å" /> | caption="1xk0, resolution 2.18Å" /> | ||
'''Crystal Structures of the G139A, G139A-NO and G143H Mutants of Human Heme Oxygenase-1'''<br /> | '''Crystal Structures of the G139A, G139A-NO and G143H Mutants of Human Heme Oxygenase-1'''<br /> | ||
==Overview== | ==Overview== | ||
Conserved glycines, Gly139 and Gly143, in the distal helix of human heme | Conserved 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. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1XK0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with HEM and NO as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | 1XK0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=HEM:'>HEM</scene> and <scene name='pdbligand=NO:'>NO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XK0 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Koshkin, A.]] | [[Category: Koshkin, A.]] | ||
[[Category: Lad, L.]] | [[Category: Lad, L.]] | ||
[[Category: Montellano, P | [[Category: Montellano, P R.Ortiz de.]] | ||
[[Category: Poulos, T | [[Category: Poulos, T L.]] | ||
[[Category: HEM]] | [[Category: HEM]] | ||
[[Category: NO]] | [[Category: NO]] | ||
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[[Category: heme degredation]] | [[Category: heme degredation]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:55:33 2008'' | ||
Revision as of 16:55, 21 February 2008
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Crystal Structures of the G139A, G139A-NO and G143H Mutants of Human Heme Oxygenase-1
OverviewOverview
Conserved 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.
DiseaseDisease
Known diseases associated with this structure: Epiphyseal dysplasia, multiple, 5 OMIM:[602109], Heme oxygenase-1 deficiency OMIM:[141250], Osteoarthritis, hand, susceptibility to OMIM:[602109], Spondyloepimetaphyseal dysplasia OMIM:[602109]
About this StructureAbout this Structure
1XK0 is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Heme oxygenase, with EC number 1.14.99.3 Full crystallographic information is available from OCA.
ReferenceReference
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
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