The prokaryotic complex iron-sulfur molybdoenzyme family

Biochim Biophys Acta. 2008 Sep;1778(9):1897-929. doi: 10.1016/j.bbamem.2007.09.002. Epub 2007 Sep 18.


Bacterial genomes encode an extensive range of respiratory enzymes that enable respiratory metabolism with a diverse group of reducing and oxidizing substrates under both aerobic and anaerobic growth conditions. An important class of enzymes that contributes to this broad diversity is the complex iron-sulfur molybdoenzyme (CISM) family. The architecture of this class comprises the following subunits. (i) A molybdo-bis(pyranopterin guanine dinucleotide) (Mo-bisPGD) cofactor-containing catalytic subunit that also contains a cubane [Fe-S] cluster (FS0). (ii) A four-cluster protein (FCP) subunit that contains 4 cubane [Fe-S] clusters (FS1-FS4). (iii) A membrane anchor protein (MAP) subunit which anchors the catalytic and FCP subunits to the cytoplasmic membrane. In this review, we define the CISM family of enzymes on the basis of emerging structural and bioinformatic data, and show that the catalytic and FCP subunit architectures appear in a wide range of bacterial redox enzymes. We evaluate evolutionary events involving genes encoding the CISM catalytic subunit that resulted in the emergence of the complex I (NADH:ubiquinone oxidoreductase) Nqo3/NuoG subunit architecture. We also trace a series of evolutionary events leading from a primordial Cys-containing peptide to the FCP architecture. Finally, many of the CISM archetypes and related enzymes rely on the tat translocon to transport fully folded monomeric or dimeric subunits across the cytoplasmic membrane. We have used genome sequence data to establish that there is a bias against the presence of soluble periplasmic molybdoenzymes in bacteria lacking an outer membrane.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Biological Evolution
  • Catalytic Domain / physiology
  • Iron-Sulfur Proteins / chemistry*
  • Iron-Sulfur Proteins / classification
  • Iron-Sulfur Proteins / metabolism*
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism
  • Models, Biological
  • Models, Molecular
  • Molecular Sequence Data
  • Molybdenum / chemistry*
  • Oxidation-Reduction
  • Periplasm / chemistry
  • Periplasm / enzymology
  • Periplasm / metabolism
  • Phylogeny
  • Prokaryotic Cells / chemistry
  • Prokaryotic Cells / enzymology*
  • Protein Subunits / chemistry
  • Protein Subunits / physiology
  • Sequence Homology, Amino Acid


  • Iron-Sulfur Proteins
  • Membrane Proteins
  • Protein Subunits
  • Molybdenum