| Discrimination between CO and O(2) in heme oxygenase: comparison of static structures and dynamic conformation changes following CO photolysis. | |
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MedLine Citation:
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PMID: 23043644 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Heme oxygenase (HO) catalyzes heme degradation, one of its products being carbon monoxide (CO). It is well known that CO has a higher affinity for heme iron than does molecular oxygen (O(2)); therefore, CO is potentially toxic. Because O(2) is required for the HO reaction, HO must discriminate effectively between CO and O(2) and thus escape product inhibition. Previously, we demonstrated large conformational changes in the heme-HO-1 complex upon CO binding that arise from steric hindrance between CO bound to the heme iron and Gly-139. However, we have not yet identified those changes that are specific to CO binding and do not occur upon O(2) binding. Here we determine the crystal structure of the O(2)-bound form at 1.8 Å resolution and reveal the structural changes that are specific to CO binding. Moreover, difference Fourier maps comparing the structures before and after CO photolysis at <160 K clearly show structural changes such as movement of the distal F-helix upon CO photolysis. No such changes are observed upon O(2) photolysis, consistent with the structures of the ligand-free, O(2)-bound, and CO-bound forms. Protein motions even at cryogenic temperatures imply that the CO-bound heme-HO-1 complex is severely constrained (as in ligand binding to the T-state of hemoglobin), indicating that CO binding to the heme-HO-1 complex is specifically inhibited by steric hindrance. The difference Fourier maps also suggest new routes for CO migration. |
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Authors:
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Masakazu Sugishima; Keith Moffat; Masato Noguchi |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-10-18 |
Journal Detail:
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Title: Biochemistry Volume: 51 ISSN: 1520-4995 ISO Abbreviation: Biochemistry Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2013-01-18 Completed Date: 2013-03-19 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 0370623 Medline TA: Biochemistry Country: United States |
Other Details:
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Languages: eng Pagination: 8554-62 Citation Subset: IM |
Affiliation:
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Department of Medical Biochemistry, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. sugishima_masakazu@med.kurume-u.ac.jp |
| Data Bank Information | |
Bank Name/Acc. No.:
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PDB/4G7L; 4G7P; 4G7T; 4G7U; 4G8P; 4G8U; 4G8W; 4G98; 4G99 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Carbon Monoxide / metabolism* Crystallography, X-Ray Heme Oxygenase (Decyclizing) / chemistry*, metabolism* Molecular Dynamics Simulation Oxygen / metabolism* Photolysis Protein Binding Protein Conformation Rats |
| Grant Support | |
ID/Acronym/Agency:
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GM036452/GM/NIGMS NIH HHS; P41 GM103543/GM/NIGMS NIH HHS; P41 RR007707/RR/NCRR NIH HHS; R01 GM036452/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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630-08-0/Carbon Monoxide; 7782-44-7/Oxygen; EC 1.14.99.3/Heme Oxygenase (Decyclizing) |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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