Dioxygen binds end-on to mononuclear copper in a precatalytic enzyme complex.
Copper active sites play a major role in enzymatic activation of dioxygen. We trapped the copper-dioxygen complex in the enzyme peptidylglycine-alphahydroxylating monooxygenase (PHM) by freezing protein crystals that had been soaked with a slow substrate and ascorbate in the presence of oxygen. The x-ray crystal structure of this precatalytic complex, determined to 1.85-angstrom resolution, shows that oxygen binds to one of the coppers in the enzyme with an end-on geometry. Given this structure, it is likely that dioxygen is directly involved in the electron transfer and hydrogen abstraction steps of the PHM reaction. These insights may apply to other copper oxygen-activating enzymes, such as dopamine beta-monooxygenase, and to the design of biomimetic complexes.
Prigge
Sean T
ST
Department of Microbiology and Molecular Immunology, The Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Eipper
Betty A
BA
Mains
Richard E
RE
Amzel
L Mario
LM
D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D020134:Catalytic Domain; D003300:Copper / Q000378:metabolism*; D003460:Crystallization; D018360:Crystallography, X-Ray; D004151:Dipeptides / Q000737:chemistry / Q000378:metabolism; D004579:Electron Transport; D005998:Glycine / Q000737:chemistry / Q000378:metabolism; D006859:Hydrogen / Q000378:metabolism; D006860:Hydrogen Bonding; D008024:Ligands; D006899:Mixed Function Oxygenases / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D011487:Protein Conformation; D051381:Rats; D014867:Water / Q000378:metabolism
D004151:Dipeptides; D008024:Ligands; D009097:Multienzyme Complexes; C485710:N-acetyl-diiodotyrosyl-threonine; D010455:Peptides; D014867:Water; D003300:Copper; D006859:Hydrogen; D006899:Mixed Function Oxygenases; C035189:peptidylglycine monooxygenase; D010100:Oxygen; D005998:Glycine