A [4Fe-4S]-Fe(CO)(CN)-L-cysteine intermediate is the first organometallic precursor in [FeFe] hydrogenase H-cluster bioassembly

Nat Chem. 2018 May;10(5):555-560. doi: 10.1038/s41557-018-0026-7. Epub 2018 Apr 9.

Abstract

Biosynthesis of the [FeFe] hydrogenase active site (the 'H-cluster') requires the interplay of multiple proteins and small molecules. Among them, the radical S-adenosylmethionine enzyme HydG, a tyrosine lyase, has been proposed to generate a complex that contains an Fe(CO)2(CN) moiety that is eventually incorporated into the H-cluster. Here we describe the characterization of an intermediate in the HydG reaction: a [4Fe-4S][(Cys)Fe(CO)(CN)] species, 'Complex A', in which a CO, a CN- and a cysteine (Cys) molecule bind to the unique 'dangler' Fe site of the auxiliary [5Fe-4S] cluster of HydG. The identification of this intermediate-the first organometallic precursor to the H-cluster-validates the previously hypothesized HydG reaction cycle and provides a basis for elucidating the biosynthetic origin of other moieties of the H-cluster.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cysteine / chemistry*
  • Electron Spin Resonance Spectroscopy
  • Hydrogen / chemistry*
  • Hydrogenase / chemistry*
  • Hydrogenase / metabolism
  • Iron-Sulfur Proteins / chemistry
  • Iron-Sulfur Proteins / economics
  • Iron-Sulfur Proteins / metabolism*
  • Molecular Structure
  • Organometallic Compounds / chemistry*

Substances

  • Iron-Sulfur Proteins
  • Organometallic Compounds
  • Hydrogen
  • iron hydrogenase
  • Hydrogenase
  • Cysteine