Structure of phenoxazinone synthase from Streptomyces antibioticus reveals a new type 2 copper center.
The multicopper oxidase phenoxazinone synthase (PHS) catalyzes the penultimate step in the biosynthesis of the antibiotic actinomycin D by Streptomyces antibioticus. PHS exists in two oligomeric forms: a dimeric form and a hexameric form, with older actinomycin-producing cultures containing predominately the hexameric form. The structure of hexameric PHS has been determined using X-ray diffraction to a resolution limit of 2.30 A and is found to contain several unexpected and distinctive features. The structure forms a hexameric ring that is centered on a pseudo 6-fold axis and has an outer diameter of 185 A with a large central cavity that has a diameter of 50 A. This hexameric structure is stabilized by a long loop connecting two domains; bound to this long loop is a fifth copper atom that is present as a type 2 copper. This copper atom is not present in any other multicopper oxidase, and its presence appears to stabilize the hexameric structure.
Department of Chemistry and Biochemistry, Arizona State University, Tempe Arizona 85287-1604, USA.
Alex W
AW
Smith
Ana
A
Camara-Artigas
Meitian
M
Wang
James P
JP
Allen
Wilson A
WA
Francisco
D003300:Copper / Q000032:analysis*; D003460:Crystallization; D004578:Electron Spin Resonance Spectroscopy; D010088:Oxidoreductases / Q000737:chemistry*; D020836:Protein Structure, Quaternary / Q000187:drug effects; D013303:Streptomyces antibioticus / Q000201:enzymology*; D014961:X-Ray Diffraction
D003300:Copper; D010088:Oxidoreductases; C023944:2-aminophenol oxidase