A proposed reaction mechanism for maize monomeric glyoxalase I

GONZALEZ, JAVIER M.; ALVAREZ, CLARISA E.; VALERIA A. CAMPOS-BERMUDEZ; KLINKE, SEBASTIÁN

San Luis

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Biofísica; 2019

Proteins: structure, dynamics and function | Lightning Talk ID:25, pág. 71.A proposed reaction mechanism for maize monomeric glyoxalase IGonzalez JM (a), Agostini RB (b), Alvarez CE (b), Klinke S (c), Andreo CS (b), Campos-Bermudez VA (b)a - INBIONATEC, CONICET, National University of Santiago del Estero. 4206, RN 9 Km 1125, Santiago delEstero, Argentinab - CEFOBI-CONICET, Centro de Estudios Fotosintéticos y Bioquímicosc - Fundación Instituto Leloir, Av Patricias Argentinas 435, (1405), Buenos Aires, ArgentinaDetoxifcation of methylglyoxal, a toxic by-product of central sugar metabolism, is amajor issue for all forms of life. The glyoxalase pathway evolved to effectively 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 confrm 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.ReferenceGonzalez, JM et al. (2019) The FEBS Journal, DOI: 10.1111/febs.14855AcknowldegmentsWe are grateful for access to the PROXIMA-2A beamline at Synchrotron SOLEIL (France), and Daniela Albanesi for her help with protein crystallization. This work was supported by funds from CONICET and ANPCyT, grants PICT 2010-0358 to V. A. C-B. and PICT 2017-4590 to J. M. G.