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PDBsum entry 4lru
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References listed in PDB file
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Key reference
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Title
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A glutathione-Independent glyoxalase of the dj-1 superfamily plays an important role in managing metabolically generated methylglyoxal in candida albicans.
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Authors
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S.Hasim,
N.A.Hussin,
F.Alomar,
K.R.Bidasee,
K.W.Nickerson,
M.A.Wilson.
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Ref.
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J Biol Chem, 2014,
289,
1662-1674.
[DOI no: ]
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PubMed id
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Abstract
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Methylglyoxal is a cytotoxic reactive carbonyl compound produced by central
metabolism. Dedicated glyoxalases convert methylglyoxal to d-lactate using
multiple catalytic strategies. In this study, the DJ-1 superfamily member ORF
19.251/GLX3 from Candida albicans is shown to possess glyoxalase activity,
making this the first demonstrated glutathione-independent glyoxalase in fungi.
The crystal structure of Glx3p indicates that the protein is a monomer
containing the catalytic triad Cys(136)-His(137)-Glu(168). Purified Glx3p has an
in vitro methylglyoxalase activity (Km = 5.5 mm and kcat = 7.8 s(-1)) that is
significantly greater than that of more distantly related members of the DJ-1
superfamily. A close Glx3p homolog from Saccharomyces cerevisiae (YDR533C/Hsp31)
also has glyoxalase activity, suggesting that fungal members of the Hsp31 clade
of the DJ-1 superfamily are all probable glutathione-independent glyoxalases. A
homozygous glx3 null mutant in C. albicans strain SC5314 displays greater
sensitivity to millimolar levels of exogenous methylglyoxal, elevated levels of
intracellular methylglyoxal, and carbon source-dependent growth defects,
especially when grown on glycerol. These phenotypic defects are complemented by
restoration of the wild-type GLX3 locus. The growth defect of Glx3-deficient
cells in glycerol is also partially complemented by added inorganic phosphate,
which is not observed for wild-type or glucose-grown cells. Therefore, C.
albicans Glx3 and its fungal homologs are physiologically relevant
glutathione-independent glyoxalases that are not redundant with the previously
characterized glutathione-dependent GLO1/GLO2 system. In addition to its role in
detoxifying glyoxals, Glx3 and its close homologs may have other important roles
in stress response.
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