4isy
Crystal structure of IscS from Mycobacterium tuberculosis
Structural highlights
FunctionISCSL_MYCTU Catalyzes the removal of elemental sulfur from cysteine to produce alanine (Probable). Participates in the biosynthesis of metalloclusters by providing the inorganic sulfur required for Fe-S core formation. One acceptor is Whib3, on which this enzyme assembles a 4Fe-4S cluster. It can use both L-cysteine and L-selenocysteine as substrates.[1] [2] Publication Abstract from PubMedThe complex multi-protein systems for the assembly of protein-bound Iron-sulfur (Fe-S) clusters are well defined in Gram-negative model organisms. Little is known about Fe-S cluster biogenesis in other bacterial species. The iron-sulfur cluster (ISC) 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 (Rv3025c) is conserved in this important pathogen. This work 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. The cysteine desulfurase IscS of Mycobacterium tuberculosis is involved in iron-sulfur cluster biogenesis and oxidative stress defense.,Rybniker J, Pojer F, Marienhagen J, Kolly GS, Chen JM, van Gumpel E, Hartmann P, Cole ST Biochem J. 2014 Feb 19. PMID:24548275[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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