Cysteine-Persulfide Sulfane Sulfur-Ligated Zn Complex of Sulfur-Carrying SufU in the SufCDSUB System for Fe-S Cluster Biosynthesis

Inorg Chem. 2024 Oct 21;63(42):19607-19618. doi: 10.1021/acs.inorgchem.4c02654. Epub 2024 Oct 9.

Abstract

SufU, a component of the SufCDSUB Fe-S cluster biosynthetic system, serves as a Zn-dependent sulfur-carrying protein that delivers inorganic sulfur in the form of cysteine persulfide from SufS to SufBCD. To understand this sulfur delivery mechanism, we studied the X-ray crystal structure of SufU and its sulfur-carrying state (persulfurated SufU) and performed functional analysis of the conserved amino acid residues around the Zn sites. Interestingly, sulfur-carrying SufU with Cys41-persulfide (Cys41-Sγ-Sδ-) exhibited a unique Zn coordination structure, in which electrophilic Sγ is ligated to Zn and nucleophilic/anionic Sδ is bound to distally conserved Arg125. This structure is distinct from those of other Cys-persulfide-Sδ-ligated metals of metalloproteins, such as hybrid cluster proteins and SoxAX. Functional analysis of SufU variants with Zn-ligand and Arg125 substitutions revealed that both Zn and Arg125 are critical for the function of SufU with SufS. The Zn-persulfide structure of SufU provides insight into the sulfur-transfer process, suggesting that persulfide-Sδ- is stabilized via bridging by Zn and Arg125 of SufU.

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry
  • Coordination Complexes / metabolism
  • Crystallography, X-Ray
  • Cysteine* / analogs & derivatives
  • Cysteine* / chemistry
  • Disulfides
  • Iron-Sulfur Proteins* / chemistry
  • Iron-Sulfur Proteins* / metabolism
  • Models, Molecular
  • Sulfides* / chemistry
  • Sulfides* / metabolism
  • Sulfur* / chemistry
  • Zinc* / chemistry

Substances

  • Cysteine
  • Zinc
  • Sulfur
  • Iron-Sulfur Proteins
  • Sulfides
  • Bacterial Proteins
  • Coordination Complexes
  • persulfides
  • cysteine persulfide
  • Disulfides