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  4. The cysteine desulfurase IscS of Mycobacterium tuberculosis is involved in iron sulfur cluster biogenesis and oxidative stress defence
 
research article

The cysteine desulfurase IscS of Mycobacterium tuberculosis is involved in iron sulfur cluster biogenesis and oxidative stress defence

Rybniker, Jan
•
Pojer, Florence  
•
Marienhagen, Jan
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2014
Biochemical Journal

The complex multiprotein systems for the assembly of protein-bound iron sulfur (Fe S) clusters are well defined in Gram-negative model organisms. However, little is known about Fe S cluster biogenesis in other bacterial species. The ISC (iron sulfur cluster) operon of Mycobacterium tuberculosis lacks several genes known to be essential for the function of this system in other organisms. However, the cysteine desulfurase IscSMtb (Rv number Rv3025c; Mtb denotes M. tuberculosis) is conserved in this important pathogen. The present study demonstrates that deleting iscSMtb renders the cells microaerophilic and hypersensitive to oxidative stress. Moreover, the Delta iscSMtb mutant shows impaired Fe S cluster-dependent enzyme activity, clearly indicating that IscSMtb is associated with Fe S cluster assembly. An extensive interaction network of IscSMtb with Fe S proteins was identified, suggesting a novel mechanism of sulfur transfer by direct interaction with apoproteins. Interestingly, the highly homologous IscS of Escherichia coli failed to complement the Delta iscSMtb mutant and showed a less diverse protein-interaction profile. To identify a structural basis for these observations we determined the crystal structure of IscSMtb, which mirrors adaptations made in response to an ISC operon devoid of IscU-like Fe S cluster scaffold proteins. We conclude that in M. tuberculosis IscS has been redesigned during evolution to compensate for the deletion of large parts of the ISC operon.

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Type
research article
DOI
10.1042/Bj20130732
Web of Science ID

WOS:000335125600004

Author(s)
Rybniker, Jan
•
Pojer, Florence  
•
Marienhagen, Jan
•
Kolly, Gaelle S.
•
Chen, Jeffrey M.
•
Van Gumpel, Edeltraud
•
Hartmann, Pia
•
Cole, Stewart T.  
Date Issued

2014

Publisher

Portland Press

Published in
Biochemical Journal
Volume

459

Start page

467

End page

478

Subjects

iron-sulfur cluster

•

IscS

•

IscU

•

protein-protein interaction

•

tuberculosis

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPCOL  
Available on Infoscience
June 16, 2014
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/104305
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