Deciphering the number and location of active sites in the monomeric glyoxalase I of Zea mays

GONZÁLEZ, JAVIER M.; AGOSTINI, ROMINA B.; ALVAREZ, CLARISA E.; KLINKE, SEBASTIÁN; ANDREO, CARLOS S.; CAMPOS-BERMUDEZ, VALERIA A.

FEBS JOURNAL

WILEY-BLACKWELL PUBLISHING, INC

Año: 2019

1742-464X

Detoxification of methylglyoxal, a toxic by-product of central sugar metabolism,is a major issue for all forms of life. The glyoxalase pathwayevolved to effectively convert methylglyoxal into D-lactate via a glutathionehemithioacetal intermediate. Recently, we have shown that the monomericglyoxalase I from maize exhibits a symmetric fold with two cavities, potentiallyharboring two active sites, in analogy with homodimeric enzyme surrogates.Here we confirm that only one of the two cavities exhibitsglyoxalase I activity and show that it adopts a tunnel-shaped structureupon substrate binding. Such conformational change gives rise to independentbinding sites for glutathione and methylglyoxal in the same active site,with important implications for the molecular reaction mechanism, whichhas been a matter of debate for several decades.