Document Detail

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.
MedLine Citation:
PMID:  21719702     Owner:  NLM     Status:  MEDLINE    
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).
Takashi Fujishiro; Osami Shoji; Shingo Nagano; Hiroshi Sugimoto; Yoshitsugu Shiro; Yoshihito Watanabe
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-06-30
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  286     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-08-22     Completed Date:  2011-10-18     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  29941-50     Citation Subset:  IM    
Department of Chemistry, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Japan.
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MeSH Terms
Amino Acid Substitution
Catalytic Domain
Crystallography, X-Ray
Hydrogen Peroxide*
Mixed Function Oxygenases / chemistry*,  genetics
Mutation, Missense
Palmitic Acid / chemistry,  metabolism
Sphingomonas / enzymology*,  genetics
Reg. No./Substance:
57-10-3/Palmitic Acid; 7722-84-1/Hydrogen Peroxide; EC 1.-/Mixed Function Oxygenases; EC 1.-/fatty acid alpha-hydroxylase

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