Catalysis and structural properties of Leishmania infantum glyoxalase II: Trypanothione specificity and phylogeny

• Type: Article in International Scientific Journal
• Date: 2008

Authors

silva, ms (Author) Other; barata, l (Author) Other; ferreira, aen (Author) Other; romao, s (Author) Other; tomas, am (Author) ICBAS; freire, ap (Author) Other; cordeiro, c (Author) Other

Journal

Title: Biochemistry

Vol. 47

Pages: 195-204

ISSN: 0006-2960

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 20 Citations

Scopus - 19 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

Other information

Authenticus ID: P-004-235

DOI: 10.1021/bi700989m

Abstract (EN): The glyoxalase pathway catalyzes the formation Of D-lactate from methylglyoxal, a toxic byproduct of glycolysis. In trypanosomatids, trypanothione replaces glutathione in this pathway, making it a potential drug target, since its selective inhibition might increase methylglyoxal concentration in the parasites. Two glyoxalase II structures were solved. One with a bound spermidine molecule (1.8 angstrom) and the other with D-lactate at the active site (1.9 angstrom). The second structure was obtained by crystal soaking with the enzyme substrate (S)-D-lactoyltrypanothione. The overall structure of Leishmania infantum glyoxalase II is very similar to its human counterpart, with important differences at the substrate binding site. The crystal structure of L. infantum glyoxalase II is the first structure of this enzyme from trypanosomatids. The differential specificity of glyoxalase II toward glutathione and trypanothione moieties was revealed by differential substrate binding. Evolutionary analysis shows that trypanosomatid glyoxalases II diverged early from eukaryotic enzymes, being unrelated to prokaryotic proteins.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10