title: Structure of Mycobacterium tuberculosis thioredoxin C.
abstract: Mycobacterium tuberculosis is a facultative intracellular parasite of alveolar macrophages. M. tuberculosis is able to propagate in harsh environments within cells such as phagocytes, despite being exposed to reactive oxygen and nitrogen intermediates. The thioredoxin redox system is conserved across the phyla and has a well characterized role in resisting oxidative stress and influencing gene expression within prokaryotic and eukaryotic cells. M. tuberculosis thioredoxin (MtbTrx) has similar functions in redox homeostasis and it has recently been shown that alkyl hydroperoxidase C is efficiently reduced to its active form by MtbTrxC, supporting this notion. To address whether the MtbTrx has similar features to other thioredoxin structures and to examine the opportunities for designing drugs against this target, MtbTrxC has been crystallized and its structure determined to 1.3 A resolution. Unexpectedly, the structure demonstrates an interesting crystal packing in which five C-terminal residues from the MtbTrxC fold insert into a groove adjacent to the active site. A very similar interaction is observed in structures of human thioredoxins bound to peptides from the target proteins NF-kappaB and Ref-1.
authors.affiliation: Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, England. paxgh@nottingham.ac.uk
authors.forename: Gareth
authors.initials: G
authors.lastname: Hall
authors.forename: Manish
authors.initials: M
authors.lastname: Shah
authors.forename: Paul A
authors.initials: PA
authors.lastname: McEwan
authors.forename: Charles
authors.initials: C
authors.lastname: Laughton
authors.forename: Malcolm
authors.initials: M
authors.lastname: Stevens
authors.forename: Andrew
authors.initials: A
authors.lastname: Westwell
authors.forename: Jonas
authors.initials: J
authors.lastname: Emsley
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D017510:Protein Folding; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D013879:Thioredoxins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D010455:Peptides; D013879:Thioredoxins