Metal-dependent inhibition of glyoxalase II: a possible mechanism to regulate the enzyme activity.
Glyoxalase II (GLX2, EC 3.1.2.6., hydroxyacylglutathione hydrolase) is a metalloenzyme involved in crucial detoxification pathways. Different studies have failed in identifying the native metal ion of this enzyme, which is expressed with iron, zinc and/or manganese. Here we report that GloB, the GLX2 from Salmonella typhimurium, is differentially inhibited by glutathione (a reaction product) depending on the bound metal ion, and we provide a structural model for this inhibition mode. This metal-dependent inhibition was shown to occur in metal-enriched forms of the enzyme, complementing the spectroscopic data. Based on the high levels of free glutathione in the cell, we suggest that the expression of the different metal forms of GLX2 during Salmonella infection could be exploited as a mechanism to regulate the enzyme activity.
Campos-Bermudez
Valeria A
VA
IBR (Instituto de Biología Molecular y Celular de Rosario), Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, S2002LRK, Rosario, Argentina. campos@cefobi-conicet.gov.ar
Morán-Barrio
Jorgelina
J
Costa-Filho
Antonio J
AJ
Vila
Alejandro J
AJ
D005978:Glutathione / Q000494:pharmacology; D007501:Iron; D007700:Kinetics; D008345:Manganese; D008667:Metalloproteins / Q000037:antagonists & inhibitors; D019216:Metals, Heavy / Q000494:pharmacology*; D012480:Salmonella Infections; D012486:Salmonella typhimurium; D013869:Thiolester Hydrolases / Q000037:antagonists & inhibitors*; D015032:Zinc; D000099301:Hydroxyacylglutathione Hydrolase
D005978:Glutathione; D007501:Iron; D008345:Manganese; D008667:Metalloproteins; D019216:Metals, Heavy; D013869:Thiolester Hydrolases; D015032:Zinc; D000099301:Hydroxyacylglutathione Hydrolase
Inorg Chem. 2005 Jul 11;44(14):4947-60
15998022
J Biol Chem. 1971 May 25;246(10):3342-55
4324897
Front Biosci. 2004 May 01;9:1035-42
14977526
Biochemistry. 2007 Oct 2;46(39):11069-79
17764159
Biochemistry. 2009 Jun 16;48(23):5426-34
19413286
Drug Metabol Drug Interact. 2008;23(1-2):13-27
18533362
J Comput Chem. 2006 Sep;27(12):1415-28
16807974
Arch Biochem Biophys. 2007 Mar 1;459(1):20-6
17196158
Arch Microbiol. 1998 Oct;170(4):209-18
9732434
Biochemistry. 1984 Dec 18;23(26):6809-16
6099143
J Biol Inorg Chem. 2004 Jun;9(4):429-38
15067523
Anal Biochem. 1989 Nov 1;182(2):319-26
2610349
Protein Sci. 2002 Mar;11(3):707-12
11847294
FEBS Lett. 2001 Aug 10;503(1):1-6
11513844
Nature. 2005 Feb 10;433(7026):657-61
15654328
Drug Metabol Drug Interact. 2008;23(1-2):29-50
18533363
Nat Struct Biol. 2000 Nov;7(11):1041-5
11062560
J Biol Chem. 2005 Aug 5;280(31):28591-600
15908436
J Inorg Biochem. 2009 Feb;103(2):274-81
19062100
Drug Metabol Drug Interact. 2008;23(1-2):125-50
18533367
Structure. 1999 Sep 15;7(9):1067-78
10508780
Proteins. 2008 Jul;72(1):531-6
18431751
J Biol Chem. 2005 Dec 9;280(49):40668-75
16227621
Biochemistry. 2005 May 24;44(20):7559-69
15895999
Arch Biochem Biophys. 1986 Mar;245(2):305-7
3006591
Biochemistry. 2007 Oct 23;46(42):11789-99
17900178
Acc Chem Res. 2006 Oct;39(10):721-8
17042472
J Biol Chem. 2001 Feb 16;276(7):4788-95
11085979
Biochem Pharmacol. 1994 Jan 20;47(2):418-20
8304987
J Am Chem Soc. 2002 Feb 6;124(5):788-805
11817955
Mol Aspects Med. 1993;14(4):287-371
8277832
J Biol Chem. 1983 Dec 10;258(23):14212-8
6315722
Infect Immun. 2002 Nov;70(11):6032-42
12379679
Ann N Y Acad Sci. 1973 Dec 31;222:539-60
4361868
Mol Microbiol. 2003 Jan;47(1):103-18
12492857
Annu Rev Microbiol. 2006;60:187-209
16704341
Biochem Pharmacol. 2007 Dec 15;74(12):1686-701
17597585
Biochemistry. 2003 Oct 14;42(40):11777-86
14529289