1ozr: Difference between revisions
New page: left|200px<br /> <applet load="1ozr" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ozr, resolution 1.74Å" /> '''Crystal Structures ... |
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'''Crystal Structures of the Ferric, Ferrous and Ferrous-NO Forms of the Asp140Ala Mutant of Human Heme Oxygenase-1: Catalytic Implications'''<br /> | '''Crystal Structures of the Ferric, Ferrous and Ferrous-NO Forms of the Asp140Ala Mutant of Human Heme Oxygenase-1: Catalytic Implications'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
1OZR 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 as [http://en.wikipedia.org/wiki/ligand ligand]. 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:// | 1OZR 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> as [http://en.wikipedia.org/wiki/ligand ligand]. 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=1OZR OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: heme oxygenase]] | [[Category: heme oxygenase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:37:55 2008'' | ||
Revision as of 17:37, 15 February 2008
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Crystal Structures of the Ferric, Ferrous and Ferrous-NO Forms of the Asp140Ala Mutant of Human Heme Oxygenase-1: Catalytic Implications
OverviewOverview
Site-directed mutagenesis studies have shown that Asp140 in both human and, rat heme oxygenase-1 is critical for enzyme activity. Here, we report the, D140A mutant crystal structure in the Fe(III) and Fe(II) redox states as, well as the Fe(II)-NO complex as a model for the Fe(II)-oxy complex. These, structures are compared to the corresponding wild-type structures. The, mutant and wild-type structures are very similar, except for the distal, heme pocket solvent structure. In the Fe(III) D140A mutant one water, molecule takes the place of the missing Asp140 carboxylate side-chain and, a second water molecule, novel to the mutant, binds in the distal pocket., Upon reduction to the Fe(II) state, the distal helix running along one, face of the heme moves closer to the heme in both the wild-type and mutant, structures thus tightening the active site. NO binds to both the wild-type, and mutant in a bent conformation that orients the NO O atom toward the, alpha-meso heme carbon atom. A network of water molecules provides a, H-bonded network to the NO ligand, suggesting a possible proton shuttle, pathway required to activate dioxygen for catalysis. In the wild-type, structure, Asp140 exhibits two conformations, suggesting a dynamic role, for Asp140 in shuttling protons from bulk solvent via the water network to, the iron-linked oxy complex. On the basis of these structures, we consider, why the D140A mutant is inactive as a heme oxygenase but active as a, peroxidase.
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
1OZR is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Heme oxygenase, with EC number 1.14.99.3 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of the ferric, ferrous, and ferrous-NO forms of the Asp140Ala mutant of human heme oxygenase-1: catalytic implications., Lad L, Wang J, Li H, Friedman J, Bhaskar B, Ortiz de Montellano PR, Poulos TL, J Mol Biol. 2003 Jul 11;330(3):527-38. PMID:12842469
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