4ISY

Crystal structure of IscS from Mycobacterium tuberculosis

Summary for 4ISY

• Entry DOI: 10.2210/pdb4isy/pdb
• Descriptor: Cysteine desulfurase, GLYCEROL, SULFATE ION, ... (4 entities in total)
• Functional Keywords: desulfurase, plp cofactor, transferase
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 4
• Total formula weight: 170819.91

Authors

Rybniker, J.,Pojer, F.,Cole, S.T. (deposition date: 2013-01-17, release date: 2014-02-26, Last modification date: 2023-12-06)

Primary citation

Rybniker, J.,Pojer, F.,Marienhagen, J.,Kolly, G.S.,Chen, J.M.,van Gumpel, E.,Hartmann, P.,Cole, S.T.
The cysteine desulfurase IscS of Mycobacterium tuberculosis is involved in iron-sulfur cluster biogenesis and oxidative stress defence.
Biochem.J., 459:467-478, 2014

PubMed 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 ∆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 ∆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.

PubMed: 24548275
DOI: 10.1042/BJ20130732

Experimental method

X-RAY DIFFRACTION (2.59 Å)