Abstract
Cytochrome P450eryF catalyzes the 6S-hydroxylation of 6-deoxyerythronolide B, the initial reaction in a multistep pathway to convert 6-deoxyerythronolide B into the antibiotic, erythromycin. The overall structure of P450eryF is similar to that of P450cam but differs in the exact positioning of several alpha-helices. The largest difference occurs in the B' helix and results in the enlargement of the substrate-binding pocket of P450eryF. The substrate is positioned with the macrolide ring perpendicular to the haem plane and contacts seven hydrophobic residues and three solvent molecules. The substrate participates in a network of hydrogen bonds that may provide a proton shuttle pathway in the oxygen cleavage reaction.
Publication types
-
Comparative Study
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Amino Acid Sequence
-
Bacterial Proteins
-
Binding Sites
-
Camphor 5-Monooxygenase
-
Catalysis
-
Cytochrome P-450 Enzyme System / chemistry*
-
Erythromycin / analogs & derivatives
-
Erythromycin / biosynthesis*
-
Erythromycin / metabolism
-
Hydrogen Bonding
-
Hydroxylation
-
Mixed Function Oxygenases / chemistry*
-
Models, Molecular*
-
Molecular Sequence Data
-
Oxygen / metabolism
-
Protein Binding
-
Protein Conformation*
-
Protein Structure, Secondary
-
Sequence Alignment
-
Sequence Homology, Amino Acid
Substances
-
Bacterial Proteins
-
6-deoxyerythronolide B
-
Erythromycin
-
Cytochrome P-450 Enzyme System
-
Mixed Function Oxygenases
-
eryF protein, Saccharopolyspora erythraea
-
Camphor 5-Monooxygenase
-
Oxygen