A Morphing [4Fe-3S-nO]-Cluster within a Carbon Monoxide Dehydrogenase Scaffold

Angew Chem Int Ed Engl. 2022 Apr 25;61(18):e202117000. doi: 10.1002/anie.202117000. Epub 2022 Mar 4.

Abstract

Ni,Fe-containing carbon monoxide dehydrogenases (CODHs) catalyze the reversible reduction of CO2 to CO. Several anaerobic microorganisms encode multiple CODHs in their genome, of which some, despite being annotated as CODHs, lack a cysteine of the canonical binding motif for the active site Ni,Fe-cluster. Here, we report on the structure and reactivity of such a deviant enzyme, termed CooS-VCh . Its structure reveals the typical CODH scaffold, but contains an iron-sulfur-oxo hybrid-cluster. Although closely related to true CODHs, CooS-VCh catalyzes neither CO oxidation, nor CO2 reduction. The active site of CooS-VCh undergoes a redox-dependent restructuring between a reduced [4Fe-3S]-cluster and an oxidized [4Fe-2S-S*-2O-2(H2 O)]-cluster. Hydroxylamine, a slow-turnover substrate of CooS-VCh , oxidizes the hybrid-cluster in two structurally distinct steps. Overall, minor changes in CODHs are sufficient to accommodate a Fe/S/O-cluster in place of the Ni,Fe-heterocubane-cluster of CODHs.

Keywords: CODH Evolution; Enzymes; Hydroxylamine Reduction; Iron-Sulfur-Oxo Cluster; Structural Biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Oxidoreductases / chemistry
  • Carbon Dioxide* / metabolism
  • Carbon Monoxide / chemistry
  • Iron-Sulfur Proteins* / metabolism
  • Multienzyme Complexes
  • Nickel / chemistry
  • Oxidation-Reduction

Substances

  • Iron-Sulfur Proteins
  • Multienzyme Complexes
  • Carbon Dioxide
  • Nickel
  • Carbon Monoxide
  • Aldehyde Oxidoreductases
  • carbon monoxide dehydrogenase