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Deciphering the number and location of active sites in the monomeric glyoxalase I of Zea mays
Author(s) -
González Javier M.,
Agostini Romina B.,
Alvarez Clarisa E.,
Klinke Sebastián,
Andreo Carlos S.,
CamposBermudez Valeria A.
Publication year - 2019
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14855
Subject(s) - methylglyoxal , lactoylglutathione lyase , active site , chemistry , glutathione , allosteric regulation , biochemistry , enzyme , protein data bank (rcsb pdb) , stereochemistry
Detoxification of methylglyoxal, a toxic by‐product of central sugar metabolism, is a major issue for all forms of life. The glyoxalase pathway evolved to effectively convert methylglyoxal into d ‐lactate via a glutathione hemithioacetal intermediate. Recently, we have shown that the monomeric glyoxalase I from maize exhibits a symmetric fold with two cavities, potentially harboring two active sites, in analogy with homodimeric enzyme surrogates. Here we confirm that only one of the two cavities exhibits glyoxalase I activity and show that it adopts a tunnel‐shaped structure upon substrate binding. Such conformational change gives rise to independent binding sites for glutathione and methylglyoxal in the same active site, with important implications for the molecular reaction mechanism, which has been a matter of debate for several decades. Database Structural data are available in The Protein Data Bank database under the accession numbers 6BNN , 6BNX , and 6BNZ .