Dioxygen Binds End-On to Mononuclear Copper in a Precatalytic Enzyme Complex

Science. 2004 May 7;304(5672):864-7. doi: 10.1126/science.1094583.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • Catalysis
  • Catalytic Domain
  • Copper / metabolism*
  • Crystallization
  • Crystallography, X-Ray
  • Dipeptides / chemistry
  • Dipeptides / metabolism
  • Electron Transport
  • Glycine / chemistry
  • Glycine / metabolism
  • Hydrogen / metabolism
  • Hydrogen Bonding
  • Ligands
  • Mixed Function Oxygenases / chemistry*
  • Mixed Function Oxygenases / metabolism*
  • Models, Molecular
  • Multienzyme Complexes / chemistry*
  • Multienzyme Complexes / metabolism*
  • Oxidation-Reduction
  • Oxygen / metabolism*
  • Peptides / metabolism
  • Protein Conformation
  • Rats
  • Water / metabolism

Substances

  • Dipeptides
  • Ligands
  • Multienzyme Complexes
  • N-acetyl-diiodotyrosyl-threonine
  • Peptides
  • Water
  • Copper
  • Hydrogen
  • Mixed Function Oxygenases
  • peptidylglycine monooxygenase
  • Oxygen
  • Glycine

Associated data

  • PDB/1SDW