4.6 Article

Structural and Biochemical Characterization of Staphylococcus aureus Cysteine Desulfurase Complex SufSU

Journal

ACS OMEGA
Volume 7, Issue 48, Pages 44124-44133

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsomega.2c05576

Keywords

-

Funding

  1. Colorado School of Mines
  2. National Science Foundation
  3. [1750624]

Ask authors/readers for more resources

In this work, the authors characterized two essential proteins involved in iron-sulfur cluster biogenesis in Staphylococcus aureus. They showed that these proteins are important in Gram-positive bacteria and focused on their potential as therapeutic targets for treating S. aureus infections. The authors provided a detailed characterization of the proteins and compared their activity to that of a related protein from Bacillus subtilis. Their results provide a basis for further investigation and the development of new treatment strategies.
In this work, we provide the first in vitro characterization of two essential proteins from Staphylococcus aureus (S. aureus) involved in iron-sulfur (Fe-S) cluster biogenesis: the cysteine desulfurase SufS and the sulfurtransferase SufU. Together, these proteins form the transient SufSU complex and execute the first stage of Fe-S cluster biogenesis in the SUFlike pathway in Gram-positive bacteria. The proteins involved in the SUF-like pathway, such as SufS and SufU, are essential in Gram-positive bacteria since these bacteria tend to lack redundant Fe-S cluster biogenesis pathways. Most previous work characterizing the SUF-like pathway has focused on Bacillus subtilis (B. subtilis). We focus on the SUF-like pathway in S. aureus because of its potential to serve as a therapeutic target to treat S. aureus infections. Herein, we characterize S. aureus SufS (SaSufS) by X-ray crystallography and UV-vis spectroscopy, and we characterize S. aureus SufU (SaSufU) by a zinc binding fluorescence assay and small-angle X-ray scattering. We show that SaSufS is a type II cysteine desulfurase and that SaSufU is a Zn2+-containing sulfurtransferase. Additionally, we evaluated the cysteine desulfurase activity of the SaSufSU complex and compared its activity to that of B. subtilis SufSU. Subsequent cross-species activity analysis reveals a surprising result: SaSufS is significantly less stimulated by SufU than BsSufS. Our results set a basis for further characterization of SaSufSU as well as the development of new therapeutic strategies for treating infections caused by S. aureus by inhibiting the SUF-like pathway.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available