Details

Autor(en) / Beteiligte

• Sukdeo, Nicole
• Daub, Elisabeth
• Honek, John F
• Sigel, Roland K. O
• Sigel, Helmut
• Sigel, Astrid

Titel

Biochemistry of the Nickel‐Dependent Glyoxalase I Enzymes

Ist Teil von

• Nickel and Its Surprising Impact in Nature, 2007, p.445-471

Ort / Verlag

Chichester, UK: John Wiley & Sons, Ltd

Erscheinungsjahr

2007

Link zum Volltext

Quelle

Wiley-Blackwell Online Books - All Titles (includes Withdrawn titles)

Beschreibungen/Notizen

• Cells have developed a highly conserved enzymatic detoxification system to neutralize the reactive and cytotoxic metabolite methylglyoxal (pyruvaldehyde). The glyoxalase system which had initially been reported in 1913 is composed of two enzymes working in tandem. Glyoxalase I (E.C. 4.4.1.5) converts the non‐enzymatically formed hemithioacetal of methylglyoxal and glutathione to the thioester S‐lactoylglutathione. This product serves as the substrate for glyoxalase II (E.C. 3.1.2.6) which hydrolyzes the thioester to D ‐lactate and regenerates the glutathione co‐substrate. Although extensive investigation of the glyoxalase I enzyme suggested a system that was Zn 2+ ‐activated, recent findings on the Escherichia coli GlxI indicate the presence of a second class of GlxI that is not activated by Zn 2+ , but is instead maximally activated in the presence of Ni 2+ . Sequence comparisons have been used to identify putative GlxI enzymes from bacterial species. Several other Ni 2+ ‐activated GlxI enzymes have been isolated and characterized from Pseudomonas aeruginosa, Neisseria meningitidis and Yersinia pestis. Crystallographic studies of the E. coli GlxI have indicated structural similarity to the Zn 2+ ‐activated GlxI from human. Given the substantial level of structural and sequence conservation between the two enzymes, it is surprising to observe a divergence in metal selectivity. This chapter reviews the critical aspects of the Ni 2+ ‐activated class of GlxI enzymes from an enzymological and biophysical perspective.