Identification of a copper-binding metallothionein in pathogenic mycobacteria.

TitleIdentification of a copper-binding metallothionein in pathogenic mycobacteria.
Publication TypeJournal Article
Year of Publication2008
AuthorsGold B, Deng H, Bryk R, Vargas D, Eliezer D, Roberts J, Jiang X, Nathan C
JournalNat Chem Biol
Date Published2008 Oct
KeywordsAmino Acid Sequence, Binding Sites, Cloning, Molecular, Copper, Gene Expression Regulation, Bacterial, Metallothionein, Molecular Sequence Data, Mycobacterium tuberculosis, Sequence Alignment

A screen of a genomic library from Mycobacterium tuberculosis (Mtb) identified a small, unannotated open reading frame (MT0196) that encodes a 4.9-kDa, cysteine-rich protein. Despite extensive nucleotide divergence, the amino acid sequence is highly conserved among mycobacteria that are pathogenic in vertebrate hosts. We synthesized the protein and found that it preferentially binds up to six Cu(I) ions in a solvent-shielded core. Copper, cadmium and compounds that generate nitric oxide or superoxide induced the gene's expression in Mtb up to 1,000-fold above normal expression. The native protein bound copper within Mtb and partially protected Mtb from copper toxicity. We propose that the product of the MT0196 gene be named mycobacterial metallothionein (MymT). To our knowledge, MymT is the first metallothionein of a Gram-positive bacterium with a demonstrated function.

Alternate JournalNat. Chem. Biol.
PubMed ID18724363
PubMed Central IDPMC2749609
Grant ListAI 62559 / AI / NIAID NIH HHS / United States
R01 AG019391-09 / AG / NIA NIH HHS / United States
R01 AG025440-04 / AG / NIA NIH HHS / United States
R37 AG019391 / AG / NIA NIH HHS / United States

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