Universität zu Köln

Rybniker, Jan, Pojer, Florence, Marienhagen, Jan ORCID: 0000-0001-5513-3730, Kolly, Gaelle S., Chen, Jeffrey M., van Gumpel, Edeltraud, Hartmann, Pia and Cole, Stewart T. (2014). The cysteine desulfurase IscS of Mycobacterium tuberculosis is involved in iron sulfur cluster biogenesis and oxidative stress defence. Biochem. J., 459. S. 467 - 479. LONDON: PORTLAND PRESS LTD. ISSN 1470-8728

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rybniker, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Pojer, Florence UNSPECIFIED UNSPECIFIED UNSPECIFIED Marienhagen, Jan UNSPECIFIED orcid.org/0000-0001-5513-3730 UNSPECIFIED Kolly, Gaelle S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Chen, Jeffrey M. UNSPECIFIED UNSPECIFIED UNSPECIFIED van Gumpel, Edeltraud UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Pia UNSPECIFIED UNSPECIFIED UNSPECIFIED Cole, Stewart T. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-439278
DOI:	10.1042/BJ20130732
Journal or Publication Title:	Biochem. J.
Volume:	459
Page Range:	S. 467 - 479
Date:	2014
Publisher:	PORTLAND PRESS LTD
Place of Publication:	LONDON
ISSN:	1470-8728
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ESCHERICHIA-COLI; TRANSFER-RNA; PROTEINS; GENE; SYSTEM; WHIB; BIOSYNTHESIS; STREPTOMYCES; HOMOLOGS; OPERON Multiple languages Biochemistry & Molecular Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43927