4LRU

Crystal structure of glyoxalase III (Orf 19.251) from Candida albicans

Summary for 4LRU

• Entry DOI: 10.2210/pdb4lru/pdb
• Descriptor: Glyoxalase III (glutathione-independent), 1,2-ETHANEDIOL, ACETATE ION, ... (4 entities in total)
• Functional Keywords: dj-1 superfamily, lyase
• Biological source: Candida albicans (yeast)
• Total number of polymer chains: 1
• Total formula weight: 26242.33

Authors

Hasim, S.,Hussin, N.A.,Nickerson, K.W.,Wilson, M.A. (deposition date: 2013-07-20, release date: 2013-08-07, Last modification date: 2023-09-20)

Primary citation

Hasim, S.,Hussin, N.A.,Alomar, F.,Bidasee, K.R.,Nickerson, K.W.,Wilson, M.A.
A Glutathione-independent Glyoxalase of the DJ-1 Superfamily Plays an Important Role in Managing Metabolically Generated Methylglyoxal in Candida albicans.
J.Biol.Chem., 289:1662-1674, 2014

PubMed Abstract: 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.

PubMed: 24302734
DOI: 10.1074/jbc.M113.505784

Experimental method

X-RAY DIFFRACTION (1.6 Å)