A novel DNA modification by sulfur: DndA is a NifS-like cysteine desulfurase capable of assembling DndC as an iron-sulfur cluster protein in Streptomyces lividans

Biochemistry. 2007 May 22;46(20):6126-33. doi: 10.1021/bi602615k. Epub 2007 May 1.


A novel DNA modification system by sulfur (S) in Streptomyces lividans 66 was reported to be encoded by a cluster of five genes designated dndA-E [Zhou, X., He, X., Liang, J., Li, A., Xu, T., Kieser, T., Helmann, J. D., and Deng, Z. (2005) Mol. Microbiol. 57, 1428-1438]. The dndA gene was cloned and the protein product expressed in Escherichia coli, purified to homogeneity, and characterized as a homodimeric protein of ca. 91 kDa. Purified DndA has a yellow color and UV-visible spectra characteristic of a pyridoxal phosphate-containing enzyme and was proven to be a cysteine desulfurase able to catalyze removal of elemental S atoms from l-cysteine to produce l-alanine with substrate specificity similar to that of E. coli IscS. DndC was also purified to homogeneity and found to contain a 4Fe-4S cluster by spectral analysis and have obvious ATP pyrophosphatase activity. DndA could catalyze iron-sulfur cluster assembly by activation of apo-Fe DndC protein prepared by removal of its iron-sulfur cluster using alpha,alpha'-dipyridyl. A mutated DndA, with serine substituted for cysteine at position 327, which was confirmed to have lost its corresponding cysteine desulfurase activity, also lost its ability to reactivate the apo-Fe DndC. The likely involvement of an interaction between DndA and DndC in the biochemical pathway for the unusual site-specific DNA modification in S. lividans 66 is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / isolation & purification
  • Carbon-Sulfur Lyases / chemistry*
  • Carbon-Sulfur Lyases / genetics
  • Carbon-Sulfur Lyases / isolation & purification
  • Carbon-Sulfur Lyases / metabolism
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / metabolism*
  • Escherichia coli Proteins / chemistry
  • Iron-Sulfur Proteins / chemistry*
  • Iron-Sulfur Proteins / genetics
  • Iron-Sulfur Proteins / isolation & purification
  • Iron-Sulfur Proteins / metabolism
  • Multigene Family*
  • Nucleotidyltransferases / chemistry
  • Oxidoreductases / chemistry
  • Protein Processing, Post-Translational* / genetics
  • Protein Subunits / chemistry
  • Sequence Homology, Amino Acid
  • Streptomyces lividans / enzymology*
  • Streptomyces lividans / genetics
  • Sulfur / chemistry


  • Bacterial Proteins
  • DNA, Bacterial
  • Escherichia coli Proteins
  • Iron-Sulfur Proteins
  • Protein Subunits
  • nifS protein, Bacteria
  • Sulfur
  • Oxidoreductases
  • 3'-phosphoadenylyl-5'-phosphosulfate reductase
  • Nucleotidyltransferases
  • sulfate adenylyltransferase (ADP)
  • Carbon-Sulfur Lyases
  • cysteine desulfurase