The octahaem MccA is a haem c-copper sulfite reductase

Nature. 2015 Apr 30;520(7549):706-9. doi: 10.1038/nature14109. Epub 2015 Feb 2.

Abstract

The six-electron reduction of sulfite to sulfide is the pivot point of the biogeochemical cycle of the element sulfur. The octahaem cytochrome c MccA (also known as SirA) catalyses this reaction for dissimilatory sulfite utilization by various bacteria. It is distinct from known sulfite reductases because it has a substantially higher catalytic activity and a relatively low reactivity towards nitrite. The mechanistic reasons for the increased efficiency of MccA remain to be elucidated. Here we show that anoxically purified MccA exhibited a 2- to 5.5-fold higher specific sulfite reductase activity than the enzyme isolated under oxic conditions. We determined the three-dimensional structure of MccA to 2.2 Å resolution by single-wavelength anomalous dispersion. We find a homotrimer with an unprecedented fold and haem arrangement, as well as a haem bound to a CX15CH motif. The heterobimetallic active-site haem 2 has a Cu(I) ion juxtaposed to a haem c at a Fe-Cu distance of 4.4 Å. While the combination of metals is reminiscent of respiratory haem-copper oxidases, the oxidation-labile Cu(I) centre of MccA did not seem to undergo a redox transition during catalysis. Intact MccA tightly bound SO2 at haem 2, a dehydration product of the substrate sulfite that was partially turned over due to photoreduction by X-ray irradiation, yielding the reaction intermediate SO. Our data show the biometal copper in a new context and function and provide a chemical rationale for the comparatively high catalytic activity of MccA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / isolation & purification
  • Bacterial Proteins / metabolism
  • Biocatalysis
  • Catalytic Domain
  • Copper / metabolism*
  • Crystallography, X-Ray
  • Cysteine / analogs & derivatives
  • Cysteine / metabolism
  • Heme / analogs & derivatives*
  • Heme / metabolism
  • Models, Molecular
  • Oxidation-Reduction
  • Oxidoreductases Acting on Sulfur Group Donors / chemistry*
  • Oxidoreductases Acting on Sulfur Group Donors / isolation & purification
  • Oxidoreductases Acting on Sulfur Group Donors / metabolism
  • Sulfites / metabolism
  • Sulfur Dioxide / metabolism
  • Wolinella / enzymology*

Substances

  • Bacterial Proteins
  • Sulfites
  • cysteine thiolate
  • Sulfur Dioxide
  • heme C
  • Heme
  • Copper
  • Oxidoreductases Acting on Sulfur Group Donors
  • Cysteine

Associated data

  • PDB/4RKM
  • PDB/4RKN