2P18

Crystal structure of the Leishmania infantum glyoxalase II

2P18 の概要

• エントリーDOI: 10.2210/pdb2p18/pdb
• 分子名称: Glyoxalase II, ZINC ION, SPERMIDINE, ... (5 entities in total)
• 機能のキーワード: metalloprotein, beta sandwich, alpha-helical domain, hydrolase
• 由来する生物種: Leishmania infantum
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34758.81

構造登録者

Trincao, J.,Barata, L.,Najmudin, S.,Bonifacio, C.,Romao, M.J. (登録日: 2007-03-02, 公開日: 2008-01-15, 最終更新日: 2023-08-30)

主引用文献

Silva, M.S.,Barata, L.,Ferreira, A.E.,Romao, S.,Tomas, A.M.,Freire, A.P.,Cordeiro, C.
Catalysis and Structural Properties of Leishmania infantum Glyoxalase II: Trypanothione Specificity and Phylogeny.
Biochemistry, 47:195-204, 2008

PubMed Abstract: 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 A) and the other with d-lactate at the active site (1.9 A). 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.

PubMed: 18052346
DOI: 10.1021/bi700989m

実験手法

X-RAY DIFFRACTION (1.8 Å)