3OO3
Crystal Structure of the Orf6* (CYP165D3) Monooxygenase Involved in Teicoplanin Biosynthesis
Summary for 3OO3
| Entry DOI | 10.2210/pdb3oo3/pdb |
| Descriptor | Oxy protein, PROTOPORPHYRIN IX CONTAINING FE (3 entities in total) |
| Functional Keywords | cytochrome p450, monooxygenase, pcd-teicoplanin aglycone, oxidoreductase |
| Biological source | Actinoplanes teichomyceticus |
| Total number of polymer chains | 1 |
| Total formula weight | 43477.54 |
| Authors | Li, Z.,Nair, S.K. (deposition date: 2010-08-30, release date: 2011-01-05, Last modification date: 2024-02-21) |
| Primary citation | Li, Z.,Rupasinghe, S.G.,Schuler, M.A.,Nair, S.K. Crystal structure of a phenol-coupling P450 monooxygenase involved in teicoplanin biosynthesis. Proteins, 79:1728-1738, 2011 Cited by PubMed Abstract: The lipoglycopeptide antibiotic teicoplanin has proven efficacy against gram-positive pathogens. Teicoplanin is distinguished from the vancomycin-type glycopeptide antibiotics, by the presence of an additional cross-link between the aromatic amino acids 1 and 3 that is catalyzed by the cytochrome P450 monooxygenase Orf6* (CYP165D3). As a goal towards understanding the mechanism of this phenol-coupling reaction, we have characterized recombinant Orf6* and determined its crystal structure to 2.2-Å resolution. Although the structure of Orf6* reveals the core fold common to other P450 monooxygenases, there are subtle differences in the disposition of secondary structure elements near the active site cavity necessary to accommodate its complex heptapeptide substrate. Specifically, the orientation of the F and G helices in Orf6* results in a more closed active site than found in the vancomycin oxidative enzymes OxyB and OxyC. In addition, Met226 in the I helix replaces the more typical Gly/Ala residue that is positioned above the heme porphyrin ring, where it forms a hydrogen bond with a heme iron-bound water molecule. Sequence comparisons with other phenol-coupling P450 monooxygenases suggest that Met226 plays a role in determining the substrate regiospecificity of Orf6*. These features provide further insights into the mechanism of the cross-linking mechanisms that occur during glycopeptide antibiotics biosynthesis. PubMed: 21445994DOI: 10.1002/prot.22996 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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