Serial Femtosecond Zero Dose Crystallography Captures a Water-Free Distal Heme Site in a Dye-Decolorising Peroxidase to Reveal a Catalytic Role for an Arginine in FeIV =O Formation

Angew Chem Int Ed Engl. 2020 Nov 23;59(48):21656-21662. doi: 10.1002/anie.202008622. Epub 2020 Sep 23.

Abstract

Obtaining structures of intact redox states of metal centers derived from zero dose X-ray crystallography can advance our mechanistic understanding of metalloenzymes. In dye-decolorising heme peroxidases (DyPs), controversy exists regarding the mechanistic role of the distal heme residues aspartate and arginine in the heterolysis of peroxide to form the catalytic intermediate compound I (FeIV =O and a porphyrin cation radical). Using serial femtosecond X-ray crystallography (SFX), we have determined the pristine structures of the FeIII and FeIV =O redox states of a B-type DyP. These structures reveal a water-free distal heme site that, together with the presence of an asparagine, imply the use of the distal arginine as a catalytic base. A combination of mutagenesis and kinetic studies corroborate such a role. Our SFX approach thus provides unique insight into how the distal heme site of DyPs can be tuned to select aspartate or arginine for the rate enhancement of peroxide heterolysis.

Keywords: X-ray serial femtosecond crystallography; arginine; bioinorganic; heme proteins; peroxidase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine / chemistry
  • Arginine / metabolism*
  • Biocatalysis
  • Coloring Agents / chemistry
  • Coloring Agents / metabolism*
  • Crystallography, X-Ray
  • Heme / chemistry
  • Heme / metabolism*
  • Iron Compounds / chemistry
  • Iron Compounds / metabolism*
  • Models, Molecular
  • Oxidation-Reduction
  • Oxygen / chemistry
  • Oxygen / metabolism*
  • Peroxidase / chemistry
  • Peroxidase / metabolism*
  • Streptomyces lividans / enzymology

Substances

  • Coloring Agents
  • Iron Compounds
  • Heme
  • Arginine
  • Peroxidase
  • Oxygen