GLO1 - Structure

Structure

Several structures of glyoxalase I have been solved. Four structures of the human form have been published, with PDB accession codes 1BH5, 1FRO, 1QIN, and 1QIP. Five structures of the Escherichia coli form have been published, with accession codes 1FA5, 1FA6, 1FA7, 1FA8, and 1F9Z. Finally, one structure of the trypanothione-specific version from Leishmania major has been solved, 2C21. In all these cases, the quaternary structure of the biological unit is a domain-swapped dimer, in which the active site and the 8-stranded beta sheet secondary structure is formed from both subunits. However, in yeast such as Saccharomyces cerevisiae, the two subunits have fused into a single monomer of double size, through gene duplication. Each half of the structural dimer is a sandwich of 3-4 alpha helices on both sides of an 8-stranded antiparallel beta sheet; the dimer interface is largely composed of the face-to-face meeting of the two beta sheets.

The tertiary and quaternary structures of glyoxalase I is similar to those of several other types of proteins. For example, glyoxalase I resembles several proteins that allow bacteria to resist antibiotics such as fosfomycin, bleomycin and mitomycin. Likewise, the unrelated enzymes methylmalonyl-CoA epimerase, 3-demethylubiquinone-9 3-O-methyltransferase and numerous dioxygenases such as biphenyl-2,3-diol 1,2-dioxygenase, catechol 2,3-dioxygenase, 3,4-dihydroxyphenylacetate 2,3-dioxygenase and 4-hydroxyphenylpyruvate dioxygenase all resemble glyoxalase I in structure. Finally, many proteins of unknown or uncertain function likewise resemble glyoxalase I, such as At5g48480 from the plant, Arabidopsis thaliana.

The active site has four major regions.