1IZO

Cytochrome P450 BS beta Complexed with Fatty Acid

Summary for 1IZO

• Entry DOI: 10.2210/pdb1izo/pdb
• Descriptor: Cytochrome P450 152A1, PROTOPORPHYRIN IX CONTAINING FE, PALMITOLEIC ACID, ... (4 entities in total)
• Functional Keywords: heme protein, protein-fatty acid complex, riken structural genomics/proteomics initiative, rsgi, structural genomics, oxidoreductase
• Biological source: Bacillus subtilis
• Total number of polymer chains: 3
• Total formula weight: 147155.88

Authors

Lee, D.S.,Yamada, A.,Sugimoto, H.,Matsunaga, I.,Ogura, H.,Ichihara, K.,Adachi, S.,Park, S.Y.,Shiro, Y.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (deposition date: 2002-10-10, release date: 2003-03-18, Last modification date: 2023-12-27)

Primary citation

Lee, D.S.,Yamada, A.,Sugimoto, H.,Matsunaga, I.,Ogura, H.,Ichihara, K.,Adachi, S.,Park, S.Y.,Shiro, Y.
Substrate Recognition and Molecular Mechanism of Fatty Acid Hydroxylation by Cytochrome P450 from Bacillus subtilis. CRYSTALLOGRAPHIC, SPECTROSCOPIC, AND MUTATIONAL STUDIES.
J.Biol.Chem., 278:9761-9767, 2003

PubMed Abstract: Cytochrome P450 isolated from Bacillus subtilis (P450(BSbeta); molecular mass, 48 kDa) catalyzes the hydroxylation of a long-chain fatty acid (e.g. myristic acid) at the alpha- and beta-positions using hydrogen peroxide as an oxidant. We report here on the crystal structure of ferric P450(BSbeta) in the substrate-bound form, determined at a resolution of 2.1 A. P450(BSbeta) exhibits a typical P450 fold. The substrate binds to a specific channel in the enzyme and is stabilized through hydrophobic interactions of its alkyl side chain with some hydrophobic residues on the enzyme as well as by electrostatic interaction of its terminal carboxylate with the Arg(242) guanidium group. These interactions are responsible for the site specificity of the hydroxylation site in which the alpha- and beta-positions of the fatty acid come into close proximity to the heme iron sixth site. The fatty acid carboxylate group interacts with Arg(242) in the same fashion as has been reported for the active site of chloroperoxidase, His(105)-Glu(183), which is an acid-base catalyst in the peroxidation reactions. On the basis of these observations, a possible mechanism for the hydroxylation reaction catalyzed by P450(BSbeta) is proposed in which the carboxylate of the bound-substrate fatty acid assists in the cleavage of the peroxide O-O bond.

PubMed: 12519760
DOI: 10.1074/jbc.M211575200

Experimental method

X-RAY DIFFRACTION (2.1 Å)