A PROPOSED REACTION MECHANISM FOR MAIZE MONOMERIC GLYOXALASE I

GONZALEZ JM; AGOSTINI RB; ALVAREZ, CE.; KLINKE, S; ANDREO CS; CAMPOS BERMUDEZ VA

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Biofísica (SAB); 2019

Detoxi􀀂cation of methylglyoxal, a toxic by􀀁product of central sugar metabolism, is amajor issue for all forms of life. The glyoxalase pathway evolved to e􀀃ectively convertmethylglyoxal into D􀀁lactate via a glutathione hemithioacetal intermediate. Recently, wehave shown that the monomeric glyoxalase I from maize exhibits a symmetric fold withtwo cavities, potentially harboring two active sites, in analogy with homodimeric enzymesurrogates. Here we con􀀂rm that only one of the two cavities exhibits glyoxalase Iactivity and show that it adopts a tunnel􀀁shaped structure upon substrate binding. Suchconformational change gives rise to independent binding sites for glutathione andmethylglyoxal in the same active site, with important implications for the molecularreaction mechanism, which has been a matter of debate for several decades.