DB code: S00185

RLCP classification	8.131.705800.452 : Isomerization
RLCP classification	8.113.585900.479 : Isomerization
CATH domain	3.10.180.10 : 2,3-Dihydroxybiphenyl 1,2-Dioxygenase; domain 1	Catalytic domain
E.C.	4.4.1.5
CSA	1fro
M-CSA	1fro
MACiE	M0032

CATH domain	Related DB codes (homologues)
3.10.180.10 : 2,3-Dihydroxybiphenyl 1,2-Dioxygenase; domain 1	D00446 D00447 D00448 S00540

Uniprot Enzyme Name
UniprotKB	Protein name	Synonyms	RefSeq	Pfam
Q04760	Lactoylglutathione lyase	EC 4.4.1.5 Methylglyoxalase Aldoketomutase Glyoxalase I Glx I Ketone-aldehyde mutase S-D-lactoylglutathione methylglyoxal lyase	NP_006699.2 (Protein) NM_006708.2 (DNA/RNA sequence)	PF00903 (Glyoxalase) [Graphical View]

KEGG enzyme name
lactoylglutathione lyase methylglyoxalase aldoketomutase ketone-aldehyde mutase glyoxylase I (R)-S-lactoylglutathione methylglyoxal-lyase (isomerizing)

UniprotKB: Accession Number	Entry name	Activity	Subunit	Subcellular location	Cofactor
Q04760	LGUL_HUMAN	(R)-S-lactoylglutathione = glutathione + methylglyoxal.	Homodimer.		Binds 1 zinc ion per subunit.

KEGG Pathways
Map code	Pathways	E.C.
MAP00620	Pyruvate metabolism

Compound table
	Cofactors	Substrates		Products	Intermediates
KEGG-id	C00038	C00051	C00546	C03451	I00019	I00020
E.C.
Compound	Zinc	Glutathione	Methylglyoxal	(R)-S-Lactoylglutathione	S-hemithiolacetal-glutathione	S-enediol-glutathione
Type	heavy metal	amino acids,carboxyl group,peptide/protein,sulfhydryl group	carbohydrate	amino acids,carbohydrate,carboxyl group,sulfide group,peptide/protein
ChEBI	29105 29105	16856 16856	17158 17158	15694 15694
PubChem	32051 32051	124886 25246407 124886 25246407	880 880	440018 440018

1bh5A	Bound:_ZN	Unbound	Unbound	Analogue:GTX	Unbound	Unbound
1bh5B	Bound:_ZN	Unbound	Unbound	Analogue:GTX	Unbound	Unbound
1bh5C	Bound:_ZN	Unbound	Unbound	Analogue:GTX	Unbound	Unbound
1bh5D	Bound:_ZN	Unbound	Unbound	Analogue:GTX	Unbound	Unbound
1froA	Bound:_ZN	Unbound	Unbound	Analogue:GSB	Unbound	Unbound
1froB	Bound:_ZN	Unbound	Unbound	Analogue:GSB	Unbound	Unbound
1froC	Bound:_ZN	Unbound	Unbound	Analogue:GSB	Unbound	Unbound
1froD	Bound:_ZN	Unbound	Unbound	Analogue:GSB	Unbound	Unbound
1qinA	Bound:_ZN	Unbound	Unbound	Unbound	Unbound	Intermediate-analogue:GIP
1qinB	Bound:_ZN	Unbound	Unbound	Unbound	Unbound	Intermediate-analogue:GIP
1qipA	Bound:_ZN	Unbound	Unbound	Analogue:GNB	Unbound	Unbound
1qipB	Bound:_ZN	Unbound	Unbound	Analogue:GNB	Unbound	Unbound
1qipC	Bound:_ZN	Unbound	Unbound	Analogue:GNB	Unbound	Unbound
1qipD	Bound:_ZN	Unbound	Unbound	Analogue:GNB	Unbound	Unbound

Reference for Active-site residues
resource	references	E.C.
Swiss-prot;Q59384, Q04760 & PDB;1fro & literature [28]

Active-site residues
PDB	Catalytic residues	Cofactor-binding residues	Modified residues	Main-chain involved in catalysis	Comment

1bh5A	GLU 99;	;GLU 99;HIS 126; (Zinc binding)			mutant Q33E,E172Q
1bh5B	GLU 99;	;GLU 99;HIS 126; (Zinc binding)			mutant Q33E,E172Q
1bh5C	GLU 99;	;GLU 99;HIS 126; (Zinc binding)			mutant Q33E,E172Q
1bh5D	GLU 99;	;GLU 99;HIS 126; (Zinc binding)			mutant Q33E,E172Q
1froA	GLU 99;GLU 172	GLN 33;GLU 99;HIS 126;GLU 172(Zinc binding)
1froB	GLU 99;GLU 172	GLN 33;GLU 99;HIS 126;GLU 172(Zinc binding)
1froC	GLU 99;GLU 172	GLN 33;GLU 99;HIS 126;GLU 172(Zinc binding)
1froD	GLU 99;GLU 172	GLN 33;GLU 99;HIS 126;GLU 172(Zinc binding)
1qinA	GLU 99;GLU 172	GLN 33;GLU 99;HIS 126;GLU 172(Zinc binding)
1qinB	GLU 99;GLU 172	GLN 33;GLU 99;HIS 126;GLU 172(Zinc binding)
1qipA	GLU 99;GLU 172	GLN 33;GLU 99;HIS 126;GLU 172(Zinc binding)
1qipB	GLU 99;GLU 172	GLN 33;GLU 99;HIS 126;GLU 172(Zinc binding)
1qipC	GLU 99;GLU 172	GLN 33;GLU 99;HIS 126;GLU 172(Zinc binding)
1qipD	GLU 99;GLU 172	GLN 33;GLU 99;HIS 126;GLU 172(Zinc binding)

References for Catalytic Mechanism
References	Sections	No. of steps in catalysis
[1]	Fig.6, p.4856-4857
[2]	Fig.6, p.10029	2
[16]	Fig.5, p.3390	3
[19]	Fig.3, p.21626-21628	3
[20]	Fig.1	2
[22]	Fig.6, p.13488-13489	2
[23]	p.93-94
[24]	p.8725-8726
[28]	Scheme 9, Scheme 13	3
[30]	Scheme 3, Scheme 4, p.10284-10289	4
[31]	Fig.4, p.6979	3

References
[1]
Resource
Comments
Medline ID
PubMed ID	7138835
Journal	Biochemistry
Year	1982
Volume	21
Pages	4850-7
Authors	Sellin S, Eriksson LE, Mannervik B
Title	Fluorescence and nuclear relaxation enhancement studies of the binding of glutathione derivatives to manganese-reconstituted glyoxalase I from human erythrocytes. A model for the catalytic mechanism of the enzyme involving a hydrated metal ion.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID	7107595
Journal	J Biol Chem
Year	1982
Volume	257
Pages	10023-9
Authors	Sellin S, Rosevear PR, Mannervik B, Mildvan AS
Title	Nuclear relaxation studies of the role of the essential metal in glyoxalase I.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID	6853506
Journal	J Biol Chem
Year	1983
Volume	258
Pages	6823-6
Authors	Rosevear PR, Chari RV, Kozarich JW, Sellin S, Mannervik B, Mildvan AS
Title	13C NMR studies of the product complex of glyoxalase I.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID	6296126
Journal	J Biol Chem
Year	1983
Volume	258
Pages	2091-3
Authors	Sellin S, Eriksson LE, Aronsson AC, Mannervik B
Title	Octahedral metal coordination in the active site of glyoxalase I as evidenced by the properties of Co(II)-glyoxalase I.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID	6547959
Journal	J Biol Chem
Year	1984
Volume	259
Pages	11436-47
Authors	Rosevear PR, Sellin S, Mannervik B, Kuntz ID, Mildvan AS
Title	NMR and computer modeling studies of the conformations of glutathione derivatives at the active site of glyoxalase I.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID	2827734
Journal	Biochemistry
Year	1987
Volume	26
Pages	6779-84
Authors	Sellin S, Eriksson LE, Mannervik B
Title	Electron paramagnetic resonance study of the active site of copper-substituted human glyoxalase I.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID	2226450
Journal	Eur J Biochem
Year	1990
Volume	193
Pages	83-90
Authors	Rae C, Berners-Price SJ, Bulliman BT, Kuchel PW
Title	Kinetic analysis of the human erythrocyte glyoxalase system using 1H NMR and a computer model.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID	1755849
Journal	Biochem Biophys Res Commun
Year	1991
Volume	181
Pages	657-63
Authors	Li J, Guha MK, Creighton DJ
Title	Enzyme chemistry of dithiohemiacetals: synthesis and characterization of S-D-dithiomandeloylglutathione as an alternate substrate for glyoxalase I.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID	2043110
Journal	Biochem Biophys Res Commun
Year	1991
Volume	177
Pages	252-8
Authors	Xie XF, Creighton DJ
Title	Synthesis and initial characterization of gamma-L-glutamyl-L-thiothreonylglycine and gamma-L-glutamyl-L-allo-thiothreonylglycine as steric probes of the active site of glyoxalase I.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID	1472100
Journal	Biochem Pharmacol
Year	1992
Volume	44
Pages	2357-63
Authors	Lo TW, Thornalley PJ
Title	Inhibition of proliferation of human leukaemia 60 cells by diethyl esters of glyoxalase inhibitors in vitro.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID	1627549
Journal	Biochemistry
Year	1992
Volume	31
Pages	6069-77
Authors	Landro JA, Brush EJ, Kozarich JW
Title	Isomerization of (R)- and (S)-glutathiolactaldehydes by glyoxalase I: the case for dichotomous stereochemical behavior in a single active site.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID	1390924
Journal	Biochim Biophys Acta
Year	1992
Volume	1159
Pages	203-8
Authors	Hamilton DS, Creighton DJ
Title	Caution: the glycylmethyl and glycylethyl esters of glutathione are substrates for glyoxalase I.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID	1459997
Journal	J Biol Chem
Year	1992
Volume	267
Pages	24933-6
Authors	Hamilton DS, Creighton DJ
Title	Inhibition of glyoxalase I by the enediol mimic S-(N-hydroxy-N-methylcarbamoyl)glutathione. The possible basis of a tumor-selective anticancer strategy.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID	8359522
Journal	Biochem Soc Trans
Year	1993
Volume	21
Pages	515-7
Authors	Mannervik B, Ridderstrom M
Title	Catalytic and molecular properties of glyoxalase I.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID	8142352
Journal	Biochemistry
Year	1994
Volume	33
Pages	3548-59
Authors	Rae C, O'Donoghue SI, Bubb WA, Kuchel PW
Title	Stereospecificity of substrate usage by glyoxalase 1: nuclear magnetic resonance studies of kinetics and hemithioacetal substrate conformation.
Related PDB
Related UniProtKB
[16]
Resource
Comments	X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
Medline ID	97361820
PubMed ID	9218781
Journal	EMBO J
Year	1997
Volume	16
Pages	3386-95
Authors	Cameron AD, Olin B, Ridderstrom M, Mannervik B, Jones TA
Title	Crystal structure of human glyoxalase I--evidence for gene duplication and 3D domain swapping.
Related PDB	1fro
Related UniProtKB	Q04760
[17]
Resource
Comments
Medline ID
PubMed ID	9671502
Journal	Biochemistry
Year	1998
Volume	37
Pages	10345-53
Authors	Saint-Jean AP, Phillips KR, Creighton DJ, Stone MJ
Title	Active monomeric and dimeric forms of Pseudomonas putida glyoxalase I: evidence for 3D domain swapping.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID	9871526
Journal	Bioorg Med Chem Lett
Year	1998
Volume	8
Pages	705-10
Authors	Ly HD, Clugston SL, Sampson PB, Honek JF
Title	Syntheses and kinetic evaluation of hydroxamate-based peptide inhibitors of glyoxalase I.
Related PDB
Related UniProtKB
[19]
Resource
Comments	X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
Medline ID	98370994
PubMed ID	9705294
Journal	J Biol Chem
Year	1998
Volume	273
Pages	21623-8
Authors	Ridderstrom M, Cameron AD, Jones TA, Mannervik B
Title	Involvement of an active-site Zn2+ ligand in the catalytic mechanism of human glyoxalase I.
Related PDB	1bh5
Related UniProtKB	Q04760
[20]
Resource
Comments
Medline ID
PubMed ID	9689946
Journal	J Theor Biol
Year	1998
Volume	193
Pages	91-8
Authors	Kalapos MP
Title	From mineral support to enzymatic catalysis--further assumptions for the evolutionary history of glyoxalase system.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID	10082363
Journal	Protein Sci
Year	1998
Volume	7
Pages	1661-70
Authors	Bergdoll M, Eltis LD, Cameron AD, Dumas P, Bolin JT
Title	All in the family: structural and evolutionary relationships among three modular proteins with diverse functions and variable assembly.
Related PDB
Related UniProtKB
[22]
Resource
Comments	X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
Medline ID	99452689
PubMed ID	10521255
Journal	Biochemistry
Year	1999
Volume	38
Pages	13480-90
Authors	Cameron AD, Ridderstrom M, Olin B, Kavarana MJ, Creighton DJ, Mannervik B
Title	Reaction mechanism of glyoxalase I explored by an X-ray crystallographic analysis of the human enzyme in complex with a transition state analogue.
Related PDB	1qin 1qip
Related UniProtKB	Q04760
[23]
Resource
Comments
Medline ID
PubMed ID	10403382
Journal	FEBS Lett
Year	1999
Volume	453
Pages	90-4
Authors	Feierberg I, Cameron AD, Aqvist J
Title	Energetics of the proposed rate-determining step of the glyoxalase I reaction.
Related PDB
Related UniProtKB
[24]
Resource
Comments	X-RAY CRYSTALLOGRAPHY.
Medline ID	20374551
PubMed ID	10913283
Journal	Biochemistry
Year	2000
Volume	39
Pages	8719-27
Authors	He MM, Clugston SL, Honek JF, Matthews BW
Title	Determination of the structure of Escherichia coli glyoxalase I suggests a structural basis for differential metal activation.
Related PDB	1f9z 1fa5 1fa6 1fa7 1fa8
Related UniProtKB	Q59384
[25]
Resource
Comments
Medline ID
PubMed ID	10801792
Journal	J Biol Chem
Year	2000
Volume	275
Pages	22657-62
Authors	Feierberg I, Luzhkov V, Aqvist J
Title	Computer simulation of primary kinetic isotope effects in the proposed rate-limiting step of the glyoxalase I catalyzed reaction.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID	11052803
Journal	J Med Chem
Year	2000
Volume	43
Pages	3981-6
Authors	Kalsi A, Kavarana MJ, Lu T, Whalen DL, Hamilton DS, Creighton DJ
Title	Role of hydrophobic interactions in binding S-(N-aryl/alkyl-N-hydroxycarbamoyl)glutathiones to the active site of the antitumor target enzyme glyoxalase I.
Related PDB
Related UniProtKB
[27]
Resource
Comments
Medline ID
PubMed ID	11212839
Journal	J Protein Chem
Year	2000
Volume	19
Pages	389-97
Authors	Stokvis E, Clugston SL, Honek JF, Heck AJ
Title	Characterization of glyoxalase I (E. coli)-inhibitor interactions by electrospray time-of-flight mass spectrometry and enzyme kinetic analysis.
Related PDB
Related UniProtKB
[28]
Resource
Comments
Medline ID
PubMed ID	11368170
Journal	Arch Biochem Biophys
Year	2001
Volume	387
Pages	1-10
Authors	Creighton DJ, Hamilton DS
Title	Brief history of glyoxalase I and what we have learned about metal ion-dependent, enzyme-catalyzed isomerizations.
Related PDB
Related UniProtKB
[29]
Resource
Comments
Medline ID
PubMed ID	11453985
Journal	Eur J Biochem
Year	2001
Volume	268
Pages	3930-6
Authors	Martins AM, Mendes P, Cordeiro C, Freire AP
Title	In situ kinetic analysis of glyoxalase I and glyoxalase II in Saccharomyces cerevisiae.
Related PDB
Related UniProtKB
[30]
Resource
Comments
Medline ID
PubMed ID	11603978
Journal	J Am Chem Soc
Year	2001
Volume	123
Pages	10280-9
Authors	Himo F, Siegbahn PE
Title	Catalytic mechanism of glyoxalase I: a theoretical study.
Related PDB
Related UniProtKB
[31]
Resource
Comments
Medline ID
PubMed ID	11459475
Journal	J Am Chem Soc
Year	2001
Volume	123
Pages	6973-82
Authors	Richter U, Krauss M
Title	Active site structure and mechanism of human glyoxalase I-an ab initio theoretical study.
Related PDB
Related UniProtKB
[32]
Resource
Comments
Medline ID
PubMed ID	11050082
Journal	J Biol Chem
Year	2001
Volume	276
Pages	1845-9
Authors	Frickel EM, Jemth P, Widersten M, Mannervik B
Title	Yeast glyoxalase I is a monomeric enzyme with two active sites.
Related PDB
Related UniProtKB
[33]
Resource
Comments
Medline ID
PubMed ID	11853416
Journal	J Am Chem Soc
Year	2002
Volume	124
Pages	1564-5
Authors	Diaconu D, Hu Z, Gorun SM
Title	Copper-based bioinspired oxygenation and glyoxalase-like reactivity.
Related PDB
Related UniProtKB
[34]
Resource
Comments
Medline ID
PubMed ID	12405831
Journal	J Am Chem Soc
Year	2002
Volume	124
Pages	13047-52
Authors	Rose IA, Nowick JS
Title	Methylglyoxal synthetase, enol-pyruvaldehyde, glutathione and the glyoxalase system.
Related PDB
Related UniProtKB

Comments
These enzymes from human and other mammal utilizes zinc ion as a cofactor, whereas the counterpart enzymes from bacteria such as E. coli (S00540 in EzCatDB) use nickel ion as a cofactor. The octahedral coordination of metal ion is essential (see [24] and [28]). This enzyme catalyzes the following reactions: (A) Addition of sulfhydryl group of glutathione to carbonyl group of methylglyoxal, forming an intermediate, hemimercaptal- or hemithioacetal-glutathione (non-enzymatic reaction): (B) Isomerization; Shift of double-bond from O=C-C to O-C=C, forming an enediol intermediate: (C) Isomerization; Shift of double-bond from C=C-O to C-C=O: According to the literature [28] and [30], the catalytic reactions for the S-enantiomer intermediate and the R-enantiomer must be different. As for the reaction for the R-enantiomer, two different mechanisms have been proposed, a "nondissociative" mechanism and a "dissociative" mechanism (see [28]). As for the S-enantiomer reaction, the reaction proceeds as follows (see [28] and [31]). (B) Isomerization; Shift of double-bond from O=C-C to O-C=C, forming an enediol intermediate: (B1) The carbonyl group (O2) and hydroxyl group (O1) of the hemiacetal intermediate are bound to zinc ion. This coordination decrease the pKa of C1-H of the intermediate, facilitating its dissociation by a general base. (In contrast, Glu172 is displaced from the zinc ion, having its own pKa value increased.) (B2) Glu172 acts as a general base to deprotonate C1-H, forming an enediolate. (C) Isomerization; Shift of double-bond from C=C-O to C-C=O: (C1) Glu172 acts as a general acid to protonate the C2 carbon, whereas Glu99 acts as a general base to deprotonate the O1 hydroxyl group. (C2) Glu99 acts as a general acid to protonate the O2 oxygen, completing the reaction. For the R-enantiomer reaction, the dissociative reaction proceeds as follows (see [30]): (B') Isomerization; Shift of double-bond from O=C-C to O-C=C, forming an enediol intermediate: (B'1) The carbonyl group (O2) and hydroxyl group (O1) of the hemiacetal intermediate are bound to zinc ion. This coordination decrease the pKa of C1-H of the intermediate, facilitating its dissociation by a general base. (B'2) Glu99 acts as a general base to deprotonate C1-H. (B'2) Glu99 acts as a general acid to protonate O2, forming an enediol intermediate. (C') Isomerization; Shift of double-bond from C=C-O to C-C=O: (C'1) Glu172 acts as a general base to deprotonate the O1 hydroxyl group. (C'2) Glu172 acts as a general acid to protonate the C2 carbon, completing the reaction. For the R-enantiomer reaction, the nondissociative reaction proceeds as follows (see [28]): (X) Elimination of glutathione from the R-enantiomer, forming an aldehyde intermediate: (Y) Addition of glutathione to the aldehyde intermediate, forming a S-enantiomer: After the formation of the S-enantiomer, the reaction follows the above reaction mechanisms, (B) and (C). However, it is not clear which of the reaction mechanisms for the R-enantiomer is adopted by this enzyme.

Comments

These enzymes from human and other mammal utilizes zinc ion as a cofactor, whereas the counterpart enzymes from bacteria such as E. coli (S00540 in EzCatDB) use nickel ion as a cofactor. The octahedral coordination of metal ion is essential (see [24] and [28]).
This enzyme catalyzes the following reactions:
(A) Addition of sulfhydryl group of glutathione to carbonyl group of methylglyoxal, forming an intermediate, hemimercaptal- or hemithioacetal-glutathione (non-enzymatic reaction):
(B) Isomerization; Shift of double-bond from O=C-C to O-C=C, forming an enediol intermediate:
(C) Isomerization; Shift of double-bond from C=C-O to C-C=O:
According to the literature [28] and [30], the catalytic reactions for the S-enantiomer intermediate and the R-enantiomer must be different. As for the reaction for the R-enantiomer, two different mechanisms have been proposed, a "nondissociative" mechanism and a "dissociative" mechanism (see [28]).
As for the S-enantiomer reaction, the reaction proceeds as follows (see [28] and [31]).
(B) Isomerization; Shift of double-bond from O=C-C to O-C=C, forming an enediol intermediate:
(B1) The carbonyl group (O2) and hydroxyl group (O1) of the hemiacetal intermediate are bound to zinc ion. This coordination decrease the pKa of C1-H of the intermediate, facilitating its dissociation by a general base. (In contrast, Glu172 is displaced from the zinc ion, having its own pKa value increased.)
(B2) Glu172 acts as a general base to deprotonate C1-H, forming an enediolate.
(C) Isomerization; Shift of double-bond from C=C-O to C-C=O:
(C1) Glu172 acts as a general acid to protonate the C2 carbon, whereas Glu99 acts as a general base to deprotonate the O1 hydroxyl group.
(C2) Glu99 acts as a general acid to protonate the O2 oxygen, completing the reaction.
For the R-enantiomer reaction, the dissociative reaction proceeds as follows (see [30]):
(B') Isomerization; Shift of double-bond from O=C-C to O-C=C, forming an enediol intermediate:
(B'1) The carbonyl group (O2) and hydroxyl group (O1) of the hemiacetal intermediate are bound to zinc ion. This coordination decrease the pKa of C1-H of the intermediate, facilitating its dissociation by a general base.
(B'2) Glu99 acts as a general base to deprotonate C1-H.
(B'2) Glu99 acts as a general acid to protonate O2, forming an enediol intermediate.
(C') Isomerization; Shift of double-bond from C=C-O to C-C=O:
(C'1) Glu172 acts as a general base to deprotonate the O1 hydroxyl group.
(C'2) Glu172 acts as a general acid to protonate the C2 carbon, completing the reaction.
For the R-enantiomer reaction, the nondissociative reaction proceeds as follows (see [28]):
(X) Elimination of glutathione from the R-enantiomer, forming an aldehyde intermediate:
(Y) Addition of glutathione to the aldehyde intermediate, forming a S-enantiomer:
After the formation of the S-enantiomer, the reaction follows the above reaction mechanisms, (B) and (C).
However, it is not clear which of the reaction mechanisms for the R-enantiomer is adopted by this enzyme.

Created	Updated
2004-05-27	2010-01-21