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.
Smith
Alex W
AW
Department of Chemistry and Biochemistry, Arizona State University, Tempe Arizona 85287-1604, USA.
Camara-Artigas
Ana
A
Wang
Meitian
M
Allen
James P
JP
Francisco
Wilson A
WA
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