1ozl: Difference between revisions
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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''' | {{Structure | ||
|PDB= 1ozl |SIZE=350|CAPTION= <scene name='initialview01'>1ozl</scene>, resolution 1.58Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene> and <scene name='pdbligand=NO:NITROGEN OXIDE'>NO</scene> | |||
|ACTIVITY= [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] | |||
|GENE= HMOX1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''Crystal Structures of the Ferric, Ferrous, and Ferrous-NO Forms of the Asp140Ala Mutant of Human Heme Oxygenase-1: Catalytic Implications''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1OZL is a [ | 1OZL is a [[Single protein]] structure of 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=1OZL OCA]. | ||
==Reference== | ==Reference== | ||
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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/12842469 12842469] | ||
[[Category: Heme oxygenase]] | [[Category: Heme oxygenase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: heme oxygenase]] | [[Category: heme oxygenase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:17:46 2008'' | ||
Revision as of 14:17, 20 March 2008
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| , resolution 1.58Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | HMOX1 (Homo sapiens) | ||||||
| Activity: | Heme oxygenase, with EC number 1.14.99.3 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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
1OZL is a Single protein structure of sequence from Homo sapiens. 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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