| Crystal structure of H2O2-dependent cytochrome P450SPalpha with its bound fatty acid substrate: insight into the regioselective hydroxylation of fatty acids at the alpha position. | |
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MedLine Citation:
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PMID: 21719702 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cytochrome P450(SPα) (CYP152B1) isolated from Sphingomonas paucimobilis is the first P450 to be classified as a H(2)O(2)-dependent P450. P450(SPα) hydroxylates fatty acids with high α-regioselectivity. Herein we report the crystal structure of P450(SPα) with palmitic acid as a substrate at a resolution of 1.65 Å. The structure revealed that the C(α) of the bound palmitic acid in one of the alternative conformations is 4.5 Å from the heme iron. This conformation explains the highly selective α-hydroxylation of fatty acid observed in P450(SPα). Mutations at the active site and the F-G loop of P450(SPα) did not impair its regioselectivity. The crystal structures of mutants (L78F and F288G) revealed that the location of the bound palmitic acid was essentially the same as that in the WT, although amino acids at the active site were replaced with the corresponding amino acids of cytochrome P450(BSβ) (CYP152A1), which shows β-regioselectivity. This implies that the high regioselectivity of P450(SPα) is caused by the orientation of the hydrophobic channel, which is more perpendicular to the heme plane than that of P450(BSβ). |
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Authors:
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Takashi Fujishiro; Osami Shoji; Shingo Nagano; Hiroshi Sugimoto; Yoshitsugu Shiro; Yoshihito Watanabe |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-06-30 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 286 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-08-22 Completed Date: 2011-10-18 Revised Date: 2011-10-19 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 29941-50 Citation Subset: IM |
Affiliation:
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Department of Chemistry, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Japan. |
| Data Bank Information | |
Bank Name/Acc. No.:
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PDB/3AWM; 3AWP; 3AWQ |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Substitution Catalytic Domain Crystallography, X-Ray Hydrogen Peroxide* Hydroxylation Mixed Function Oxygenases / chemistry*, genetics Mutation, Missense Palmitic Acid / chemistry, metabolism Sphingomonas / enzymology*, genetics |
| Chemical | |
Reg. No./Substance:
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57-10-3/Palmitic Acid; 7722-84-1/Hydrogen Peroxide; EC 1.-/Mixed Function Oxygenases; EC 1.-/fatty acid alpha-hydroxylase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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