Enlightening the molecular basis of trypanothione specificity in trypanosomatids: Mutagenesis of Leishmania infantum glyoxalase II

• Type: Article in International Scientific Journal
• Date: 2011

Authors

barata, l (Author) Other; silva, ms (Author) Other; schuldt, l (Author) Other; ferreira, aen (Author) Other; gomes, ra (Author) Other; tomas, am (Author) FCUP; weiss, ms (Author) Other; freire, ap (Author) Other; cordeiro, c (Author) Other

Journal

Title: Experimental Parasitology

Vol. 129

Pages: 402-408

ISSN: 0014-4894

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 5 Citations

Scopus - 5 Citations

Scientific classification

FOS: Medical and Health sciences > Health sciences

Other information

Authenticus ID: P-002-J78

DOI: 10.1016/j.exppara.2011.08.008

Abstract (EN): Leishmania infantum glyoxalase II shows absolute specificity towards its trypanothione thioester substrate. In the previous work, we performed a comparative analysis of glyoxalase II structures determined by X-ray crystallography which revealed that Tyr291 and Cys294, absent in the human homologue, are essential for substrate binding. To validate this trypanothione specificity hypothesis we produced a mutant L. infantum GLO2 enzyme by replacing Tyr291 and Cys294 by arginine and lysine, respectively. This new enzyme is capable to use the glutathione thioester substrate, with kinetic parameters similar to the ones from the human enzyme. Substrate specificity is likely to be mediated by spermidine moiety binding, providing a primer for understanding the molecular basis of trypanothione specificity. (C) 2011 Elsevier Inc. All rights reserved.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7