PDBsum entry 4lru

Lyase

PDB id: 4lru

Contents

Protein chain

239 a.a.

Ligands

EDO

ACT

Waters ×279

PDB id:

4lru

Name:

Lyase

Title:

Crystal structure of glyoxalase iii (orf 19.251) from candida albicans

Structure:

Glyoxalase iii (glutathione-independent). Chain: a. Engineered: yes

Source:

Candida albicans. Yeast. Organism_taxid: 237561. Strain: sc5314. Gene: cao19.7882, orf 19.251, orf19.7882. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.60Å R-factor: 0.159 R-free: 0.185

Authors:

S.Hasim,N.A.Hussin,K.W.Nickerson,M.A.Wilson

Key ref:

S.Hasim et al. (2014). 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. PubMed id: 24302734 DOI: 10.1074/jbc.M113.505784

Date:

20-Jul-13 Release date: 07-Aug-13

Protein chain

Q5AF03  (HSP31_CANAL) -  Glyoxalase 3 from Candida albicans (strain SC5314 / ATCC MYA-2876)

Seq: 236 a.a.

Struc: 239 a.a.

Enzyme reactions

• Enzyme class: E.C.4.2.1.130 - D-lactate dehydratase.
• Reaction: methylglyoxal + H2O = (R)-lactate + H⁺

methylglyoxal + H2O (Bound ligand (Het Group name = EDO) matches with 80.00% similarity) = (R)-lactate + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1074/jbc.M113.505784

J Biol Chem 289:1662-1674 (2014)

PubMed id: 24302734

A glutathione-independent glyoxalase of the DJ-1 superfamily plays an important role in managing metabolically generated methylglyoxal in Candida albicans.

S.Hasim, N.A.Hussin, F.Alomar, K.R.Bidasee, K.W.Nickerson, M.A.Wilson.

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.