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2.5.1.18: glutathione transferase

This is an abbreviated version!
For detailed information about glutathione transferase, go to the full flat file.

Word Map on EC 2.5.1.18

Reaction

RX
+
glutathione
=
HX
 +
R-S-glutathione

Synonyms

2-hydroxychromene-2-carboxylic acid isomerase, 26GST, adGSTD4-4, agGSTe2, allergen Der p 2, allergen Der p 8, alpha class glutathione transferase, Alpha class GST, alpha GST, alpha-class glutathione transferase, asGST5.5, AtGSTF2, AtuGSTH1-1, BaeAB, beta-etherase, bmGSTD, BphK, CgGSTM1, CgGSTM2, cGST, Chi class GST, Chi GST, class mu glutathione S-transferase, delta class glutathione transferase, delta-class glutathione S-transferase, Delta-class glutathione transferase, EC 1.8.6.1, EC 2.5.1.12, EC 2.5.1.13, EC 2.5.1.14, EC 4.4.1.7, EGST, epsilon class GST, Epsilon glutathione S-transferase, Epsilon glutathione transferase, Epsilon GST, epsilon-class glutathione S-transferase, epsilon-class glutathione transferase, GHR, glutathione S-alkyl transferase, glutathione S-aralkyltransferase, glutathione S-aryltransferase, glutathione S-transferase, glutathione S-transferase 2, glutathione S-transferase A1-1, glutathione S-transferase A3-3, glutathione S-transferase AdFSTD3-3, glutathione S-transferase I, glutathione S-transferase omega 1, glutathione S-transferase omega 2, glutathione S-transferase P1-1, glutathione S-transferase pi, glutathione S-transferase Pi-1, glutathione S-transferase X, glutathione transferase, glutathione transferase A1-1, glutathione transferase A4-4, glutathione transferase M1-1, glutathione transferase M2-2, glutathione transferase Omega 3S, glutathione transferase omega-1, glutathione transferase P1-1, glutathione transferase Pi, glutathione transferase T1-1, glutathione transferase zeta, glutathione transferase zeta 1, glutathione transferase Zeta 1-1, glutathione transferase zeta1-1, glutathione transferase-like protein, glutathione-S-transferas, glutathione-S-transferase, glutathione-S-transferase pi, glutathione-transferase, GmGSTU4-4, GSH S-transferase, GSH transferase, GSH transferase homologue, GSH-S transferase rho, GSHTase-P, GST, GST A1-1, GST A2-2, GST A3-3, GST A4-4, GST adgstD4-4, GST alpha, GST Delta 2, GST I, GST II, GST III, GST IV, GST M1-1, GST M2-2, GST M4-4, GST M5-5, GST mu, GST O1-1, GST P1-1, GST pi, GST T1-1, GST Tau, GST Tau19, GST Z1-1, GST-1, GST-2, GST-26, GST-3, GST-Acr, GST-OCX-32, GST-T, GST-theta, GST1, GST1b, GST2, GST20, GST3, GST4, GST5, GST5118, GST7, GST83044, Gsta, GSTA1, GSTA1-1, GSTA2-2, GSTA3, GSTA3-3, GSTA4, GSTA4-4, GSTA4L, GSTA5, GSTA5-5, GSTalpha1, GSTD, GSTD1, GSTD10, GSTd14, GSTD2, GSTD4, GSTD4-4, GSTE1, GSTE2, GSTE3, GSTE4, GSTE5, GSTE6, GSTE7, GSTE8, GSTF12-1, GSTF12-2, GSTF3, GSTF5, GSTF9, GSTFuA1, GSTk, GSTK1, GSTL1, GSTL2, GSTL3, Gstm, GSTm09, GSTM1, GSTM1-1, GSTM2, GSTM2-2, GSTM3, GSTM3-3, GSTM4, GSTM4-4, GSTM5, GSTM5-5, GSTmu, GSTO, GSTO1, GSTO1-1, GSTO2, GSTO2-2, GstO2A, GstO2B, GSTO3, GSTO3S, GSTO4, GSTO7, GSTP, GSTP 1-1, GSTP-1, GSTP1, GSTP1-1, Gstr1, GSTrho, GSTS, GSTS1, GSTS1-1, GSTS2, GSTS3, GSTT, GSTT1, GSTT1-1, Gstt1a, GSTT2, GSTT2-2, GSTT2B-2B, GSTT4, GSTT4L, GSTU1, GSTU10, GSTU10-10, GSTU11, GSTU12, GSTU13, GSTU13-1, GSTU14, GSTU16, GSTU17, GSTU18, GSTU19, GSTU2, GSTU2-2, GSTU21, GSTU24, GSTU24-1, GSTU25, GSTU26, GSTU28, GSTU3, GSTU4, GSTU45, GSTU5, GSTU6, GSTU7, GSTU8, GSTU9, GSTZ, Gstz1, GSTZ1-1, GTT1.2, HCCA isomerase, Hematopoietic prostaglandin D synthase, hGSTA-3, hGSTA1-1, hGSTZ1-1, kappa class glutathione transferase, kappa class GSH transferase, Kappa class GST, KKSG9, lambda glutathione transferase, MAAI, MGST1, MGST2, MGST3, Mgst3a, Mgst3b, microsomal glutathione transferase 1, microsomal glutathione transferase-1, More, mtMGST1, mu class glutathione S-transferase, Mu class GST, mu glutathione transferase, Mu GST, mu-class glutathione S-transferase, mu-class glutathione S-transferase1, Mu-class GST, Mu-GST, nu-class glutathione transferase, Omega class GST, omega glutathione S-transferase, omega glutathione transferase, omega-class glutathione S-transferase, omega-class glutathione S-transferase 2, pGSTA1, phi class glutathione transferase, Pi class GST, pm-GSTR1, PmGST, PtGSTU1, PvGSTF1-1, PvGSTU2-2, PvGSTU3-3, rho class glutathione S-transferase, rho-GST, RX: glutathione R-transferase, RX:glutathione R-transferase, S-(hydroxyalkyl)glutathione lyase, Saro_2873/Saro_2872, selenium-containing glutathione transferase zeta1-1, seleno-hGSTZ1-1, SGST26.5, sigma class glutathione transferase, Sigma class GST, sigma glutathione S-transferase, sigma-class glutathione S-transferase, sigma-class GST, SIGST, Sj26GST, sjGST, sll1545, ssGST3, ssGST5, tau class glutathione S-transferase, tau class glutathione transferase, tau class GST, tau class GSTU4-4, TDR1, theta class glutathione S-transferase, theta class glutathione transferase T1-1, theta class GST, theta-class glutathione transferase, thiol-dependent reductase I, Ure2p mutant A122C, Ure2pB1, Xi class glutathione transferase, Ya-GST, YghU, zeta class glutathione S-transferase, Zeta class GST

ECTree

     2 Transferases
         2.5 Transferring alkyl or aryl groups, other than methyl groups
             2.5.1 Transferring alkyl or aryl groups, other than methyl groups (only sub-subclass identified to date)
                2.5.1.18 glutathione transferase

Engineering

Engineering on EC 2.5.1.18 - glutathione transferase

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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Y12C
the mutant displays low catalytic activity and dehalogenation function against all the substrates when compared with the wild type enzyme. The mutant displays a higher affinity for 4-nitrobenzyl chloride when compared with the wild type, however, no significant change in glutathione affinity is observed
F22A
-
site-directed mutagenesis, the mutant shows reduced glutathione transferase activity and increased glutatione peroxidase activity compared to the wild-type GSTH1-1
R187A
-
site-directed mutagenesis, the mutant shows reduced glutathione transferase activity and reduced glutatione peroxidase activity compared to the wild-type GSTH1-1
R34A
-
site-directed mutagenesis, almost inactive mutant
S25A
-
site-directed mutagenesis, the mutant shows reduced glutathione transferase activity and increased glutatione peroxidase activity compared to the wild-type GSTH1-1
F22A
Agrobacterium tumefaciens C58 / ATCC 33970
-
site-directed mutagenesis, the mutant shows reduced glutathione transferase activity and increased glutatione peroxidase activity compared to the wild-type GSTH1-1
-
R187A
Agrobacterium tumefaciens C58 / ATCC 33970
-
site-directed mutagenesis, the mutant shows reduced glutathione transferase activity and reduced glutatione peroxidase activity compared to the wild-type GSTH1-1
-
R34A
Agrobacterium tumefaciens C58 / ATCC 33970
-
site-directed mutagenesis, almost inactive mutant
-
S25A
Agrobacterium tumefaciens C58 / ATCC 33970
-
site-directed mutagenesis, the mutant shows reduced glutathione transferase activity and increased glutatione peroxidase activity compared to the wild-type GSTH1-1
-
D150A
-
turnover-number for reaction with reduced glutathione and 1-chloro-2,4-dinitrobenzene is 1.3fold higher than wild-type value. KM-value for 1-chloro-2,4-dinitrobenzene is 2fold higher than wild-type value
D150S
-
turnover-number for reaction with reduced glutathione and 1-chloro-2,4-dinitrobenzene is 1.1fold higher than wild-type value. KM-value for 1-chloro-2,4-dinitrobenzene is 2fold higher than wild-type value
D150Y
-
turnover-number for reaction with reduced glutathione and 1-chloro-2,4-dinitrobenzene is 1.2fold higher than wild-type value. KM-value for 1-chloro-2,4-dinitrobenzene is 1.7fold higher than wild-type value
E37A
-
half-life at 45°C is 1.73 min, compared to 15.3 min for wild-type enzyme. Turnover-number for reaction with reduced glutathione and 1-chloro-2,4-dinitrobenzene is 1.3fold lower than wild-type value
E37Q
-
half-life at 45°C is 6.54 min, compared to 15.3 min for wild-type enzyme. Turnover-number for reaction with reduced glutathione and 1-chloro-2,4-dinitrobenzene is nearly identical to wild-type value
F123A
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
F123E
site-directed mutagenesis, the mutant shows a negative effect on enzyme catalysis through either catalytic rate or binding affinity influence, but increased stability compared to the wild-type enzyme
F123X
site-directed mutagenesis, the mutants show reduced activity compared to the wild-type enzyme
F212A
decreased activity towards 1-chloro-2,4-dinitrobenzene compared to the wild type enzyme
F212E
decreased activity towards 1-chloro-2,4-dinitrobenzene compared to the wild type enzyme
F212H
decreased activity towards 1-chloro-2,4-dinitrobenzene compared to the wild type enzyme
F212L
decreased activity towards 1-chloro-2,4-dinitrobenzene compared to the wild type enzyme
F212W
decreased activity towards 1-chloro-2,4-dinitrobenzene compared to the wild type enzyme
F212Y
decreased activity towards 1-chloro-2,4-dinitrobenzene compared to the wild type enzyme
F216A
decreased activity towards 1-chloro-2,4-dinitrobenzene compared to the wild type enzyme
H144A
-
turnover-number for reaction with reduced glutathione and 1-chloro-2,4-dinitrobenzene is 1.2fold higher than wild-type value. KM-value for 1-chloro-2,4-dinitrobenzene is nearly identical to wild-type value
I52A
-
half-life at 45°C is 9.58 min, compared to 15.3 min for wild-type enzyme. Turnover-number for reaction with reduced glutathione and 1-chloro-2,4-dinitrobenzene is 100fold lower than wild-type value
I52L
-
half-life at 45°C is 18.1 min, compared to 15.3 min for wild-type enzyme. Turnover-number for reaction with reduced glutathione and 1-chloro-2,4-dinitrobenzene is 1.4fold lower than wild-type value
L103E
-
the ratio of turnover number to KM-value for 1-chloro-2,4-dinitrobenzene is 1.8fold higher than wild-type ratio, the ratio of turnover number to KM-value for GSH is 2.9fold lower than wild-type ratio. Half-life of mutant enzyme at 45°C is below 1 min, compared to half-life of wild-type enzyme, which is about 13 min
L103I
-
the ratio of turnover number to KM-value for 1-chloro-2,4-dinitrobenzene is 3fold higher than wild-type ratio, the ratio of turnover number to KM-value for GSH is 2.7fold lower than wild-type ratio. Half-life of mutant enzyme at 45°C is below 1 min, compared to half-life of wild-type enzyme, which is about 13 min
L103M
-
the ratio of turnover number to KM-value for 1-chloro-2,4-dinitrobenzene is 3.6fold higher than wild-type ratio, the ratio of turnover number to KM-value for GSH is 5.7fold lower than wild-type ratio. Increased half-life at 45°C as compared to wild-type enzyme
L103N
-
expressed as insoluble inclusion bodies in Escherichia coli. The ratio of turnover number to KM-value for 1-chloro-2,4-dinitrobenzene is 1.15fold higher than wild-type ratio, the ratio of turnover number to KM-value for GSH is 44.3fold lower than wild-type ratio. Half-life of mutant enzyme at 45°C is below 1 min, compared to half-life of wild-type enzyme, which is about 13 min
L103R
-
the ratio of turnover number to KM-value for 1-chloro-2,4-dinitrobenzene is fold higher than wild-type ratio, the ratio of turnover number to KM-value for GSH is fold lower than wild-type ratio. Half-life of mutant enzyme at 45°C is below 1 min, compared to half-life of wild-type enzyme, which is about 13 min
L103Y
-
expressed as insoluble inclusion bodies in Escherichia coli. The ratio of turnover number to KM-value for 1-chloro-2,4-dinitrobenzene is fold higher than wild-type ratio, the ratio of turnover number to KM-value for GSH is fold lower than wild-type ratio. Half-life of mutant enzyme at 45°C is below 1 min, compared to half-life of wild-type enzyme, which is about 13 min
L104A
-
the ratio of turnover number to KM-value for 1-chloro-2,4-dinitrobenzene is 1.3fold higher than wild-type ratio, the ratio of turnover number to KM-value for GSH is 33.3fold lower than wild-type ratio. Half-life of mutant enzyme at 45°C is below 1 min, compared to half-life of wild-type enzyme, which is about 13 min
L33A
-
half-life at 45°C is 45.3 min, compared to 15.3 min for wild-type enzyme. Turnover-number for reaction with reduced glutathione and 1-chloro-2,4-dinitrobenzene is 2.7fold lower than wild-type value
L33F
-
half-life at 45°C is 212 min, compared to 15.3 min for wild-type enzyme. Turnover-number for reaction with reduced glutathione and 1-chloro-2,4-dinitrobenzene is 40.2fold lower than wild-type value
L33I
-
half-life at 45°C is 30.4 min, compared to 15.3 min for wild-type enzyme. Turnover-number for reaction with reduced glutathione and 1-chloro-2,4-dinitrobenzene is 1.2fold lower than wild-type value
L33Y
-
half-life at 45°C is 71.7 min, compared to 15.3 min for wild-type enzyme. Turnover-number for reaction with reduced glutathione and 1-chloro-2,4-dinitrobenzene is 186fold lower than wild-type value
L6A
-
half-life at 45°C is 1.73 min, compared to 15.3 min for wild-type enzyme. Turnover-number for reaction with reduced glutathione and 1-chloro-2,4-dinitrobenzene is 1.5fold lower than wild-type value
Q112A
slightly decreased activity towards 1-chloro-2,4-dinitrobenzene compared to the wild type enzyme
R214A
decreased activity towards 1-chloro-2,4-dinitrobenzene compared to the wild type enzyme
R96A
-
turnover-number for reaction with reduced glutathione and 1-chloro-2,4-dinitrobenzene is 1.9fold higher than wild-type value. KM-value for 1-chloro-2,4-dinitrobenzene is 1.5fold higher than wild-type value
T174A
decreased activity towards 1-chloro-2,4-dinitrobenzene compared to the wild type enzyme
T31A
-
half-life at 45°C is 22.7 min, compared to 15.3 min for wild-type enzyme. Turnover-number for reaction with reduced glutathione and 1-chloro-2,4-dinitrobenzene is 2.7fold lower than wild-type value
V107A
-
site-directed mutagenesis, highly stable enzyme mutant
V147A
-
turnover-number for reaction with reduced glutathione and 1-chloro-2,4-dinitrobenzene nearly identical to wild-type value. KM-value for 1-chloro-2,4-dinitrobenzene is 1.5fold lower than wild-type value
V147L
-
turnover-number for reaction with reduced glutathione and 1-chloro-2,4-dinitrobenzene is 1.2fold lower than wild-type value. KM-value for 1-chloro-2,4-dinitrobenzene is 1.8fold lower than wild-type value
Y111A
site-directed mutagenesis, the mutant shows a decreased kcat, but unaltered Km, compared to the wild-type enzyme
Y111E
site-directed mutagenesis, the mutant shows an approximately 14fold decreased GSH binding affinity, 225fold decreased catalytic efficiency, and a 15fold decreased kcat, but increased stability, relative to the wild-type enzyme. The 1,2-dichloro-4-nitrobenzene binding affinity is also decreased approximately 2.6fold relative to the wild-type enzyme probably due to conformational rearrangement of the H-site
Y111F
site-directed mutagenesis, the mutant shows a decreased kcat, but unaltered Km, compared to the wild-type enzyme
Y111H
site-directed mutagenesis, the mutant shows a slightly different catalytic rate compared to the wild-type enzyme, but the enzyme displays 4fold lower binding affinity towards GSH, as well as positive cooperativity
Y111S
site-directed mutagenesis, the mutant shows a decreased kcat, but unaltered Km, compared to the wild-type enzyme
Y118A
site-directed mutagenesis, the mutant shows 6.8fold increased half-life compared to the wild-type enzyme
Y119A
site-directed mutagenesis, the mutant is similar to the wild-type enzyme
Y119E
site-directed mutagenesis, the mutant shows 2-3fold reduced substrate binding affinity, but increased stability, compared to the wild-type enzyme
Y119F
site-directed mutagenesis, the mutant shows 18fold increased activity compared to the wild-type enzyme with substrate 1,2-dichloro-4-nitrobenzene, and a 9fold greater substrate binding affinity compared to the wild-type enzyme
Y119H
site-directed mutagenesis, the mutant is similar to the wild-type enzyme
Y119S
site-directed mutagenesis, the mutant shows 2-3fold reduced substrate binding affinity compared to the wild-type enzyme
Y215A
decreased activity towards 1-chloro-2,4-dinitrobenzene compared to the wild type enzyme
Y215E
decreased activity towards 1-chloro-2,4-dinitrobenzene compared to the wild type enzyme
Y215F
increased activity towards 1-chloro-2,4-dinitrobenzene compared to the wild type enzyme
Y215H
decreased activity towards 1-chloro-2,4-dinitrobenzene compared to the wild type enzyme
Y215S
decreased activity towards 1-chloro-2,4-dinitrobenzene compared to the wild type enzyme
C19Y
-
random mutagenesis, inactive mutant
K30E
-
site-directed mutagenesis, inactive mutant
K83E
-
random mutagenesis, the mutant shows 50% reduced activity compared to the wild-type enzyme
L11P
-
site-directed mutagenesis, inactive mutant
L11P/I140T
-
site-directed mutagenesis, inactive mutant
L147F
-
random mutagenesis, the mutant shows 47.7% reduced activity compared to the wild-type enzyme
L147P
-
site-directed mutagenesis, inactive mutant
L150P
-
site-directed mutagenesis, inactive mutant
L169R
-
site-directed mutagenesis, inactive mutant
L27P
-
site-directed mutagenesis, inactive mutant
L80P/N116S
-
site-directed mutagenesis, inactive mutant
P61S
-
random mutagenesis, inactive mutant
Q102R
-
random mutagenesis, the mutant shows 68.4% reduced activity compared to the wild-type enzyme
Q112R
-
random mutagenesis, inactive mutant
R22H/K83E
-
random mutagenesis, inactive mutant
S105R/Q213R
-
site-directed mutagenesis, inactive mutant
S109P
-
random mutagenesis, inactive mutant
S73P
-
random mutagenesis, inactive mutant
S73X
-
site-directed mutagenesis, inactive mutant
W15R
-
random mutagenesis, inactive mutant
H52A
-
site-directed mutagensis, the mutant shows reduced activity compared to the wild-type enzyme
Q51A
-
site-directed mutagensis, the mutant shows reduced activity compared to the wild-type enzyme
R68A
-
site-directed mutagensis, inactive mutant
S11A
-
site-directed mutagensis, the mutant shows reduced activity compared to the wild-type enzyme
S67A
-
site-directed mutagensis, the mutant shows reduced activity compared to the wild-type enzyme
C10A
the mutation causes the preferential binding of glutathione to the H-site, the mutant shows a decrease in activity of about 50%, drastic increase in Km value for glutathione of 105fold, and 23fold lower catalytic efficiency compared to the wild type enzyme
C10A/S11A
mutant shows dramatic decrease in specific activity of about 98%, the double mutation exhibits loss of affinity for glutathione, a Km value 10-fold higher than in the wild type, and a 291fold decrease of the catalytic efficiency compared to the wild type enzyme
E46Q/E106K/I149V/N!60Y/H167R/R184K
-
naturally occuring polymorphisms, nucleotide difference between isozymes Der p 8 and Der p 2, overview
C10A
shows a 5 or 6fold higher kcat than wild type for both glutathione and 1-chloro-2,4-dinitrobenzene, accompanied by an 8fold increase in the Km for glutathione
C10S
shows a 25fold lower kcat for glutathione H and 5fold lower kcat for 1-chloro-2,4-dinitrobenzene than wild type accompanied by a 6fold decrease in the Km for glutathione
H106A
shows clearly decreased activity compared to the wild type enzyme
H106F
shows decreased activity compared to the wild type enzyme
F136A
the mutation drastically increases the protein activity to more than 1.5fold. Both binding affinity and catalytic efficiency of the mutant enzyme to the substrates 1-chloro-2,4-dinitrobenzene as well as glutathione are increased compared to the wild type enzyme
N22A
the mutant shows reduced activity towards 1-chloro-2,4-dinitrobenzene and increased activity towards 5-chloromethylfluorescein diacetate compared to the wild type enzyme
N24A
the mutant shows no activity towards 1-chloro-2,4-dinitrobenzene and alpha-O-(beta-methylumbelliferyl)acetovanillone and increased activity towards 5-chloromethylfluorescein diacetate and cumene hydroperoxide compared to the wild type enzyme
Y46A
the mutant shows no activity towards 1-chloro-2,4-dinitrobenzene and increased activity towards 5-chloromethylfluorescein diacetate compared to the wild type enzyme
N48A
site-directed mutagensiss of a strictly conserved residue, the mutation significantly affects substrate binding and specificity. Mutation of Asn48 and Pro49 residues may bring about secondary effects altering the thermal stability and the catalytic activity (kcat) of the enzyme without affecting the nature of the rate-limiting step of the catalytic reaction
P49A
site-directed mutagensiss of a strictly conserved residue, the mutation significantly affects substrate binding and specificity. Mutation of Asn48 and Pro49 residues may bring about secondary effects altering the thermal stability and the catalytic activity (kcat) of the enzyme without affecting the nature of the rate-limiting step of the catalytic reaction
S13A
site-directed mutagensiss of a strictly conserved residue, the mutation significantly affects substrate binding and specificity
A113V
wild type specific activity with 1-chloro-2,4-dinitrobenzene
A140D
naturally occuring mutation, most common missense polymorphism found in each of the populations studied so far, the substitution involves a charge change it does not seem to have a significant effect on enzymatic activity with a range of substrates
A236V
naturally occuring mutation, the substitution occurs in individuals from Chile and Mexico
A85S
a naturally occuring polymorphism in Caucasian population
C115A
-
mutant displays significant decrease in 1-chloro-2,4-dinitrobenzene activity
C130Y
naturally occuring mutation, the substitution is rare and may generate unstable protein
C14A/C47A/C101A
mutant shows 92% decrease in the specific activity towards 1-chloro-2,4-dinitrobenzene compared to the His-tagged wild type enzyme
C14A/C47A/C101A/C169A
mutant shows 96% decrease in the specific activity towards 1-chloro-2,4-dinitrobenzene compared to the His-tagged wild type enzyme
C14S/T226I/W234R
-
construction of chimeric mutant F2:1215 comprising sequences from the human isozymes GST-T1-1 and GST-T2, as well as from the GST-T1-1 of Mus musculus, the mutant F2:1215 shows highly increased activity compared to the human enzyme and increased activity compared to the murine enzyme, overview
C16A
-
mutation causes a high increase in the KM-value. Mutation diminishes activity with both chlorofluoroacetic acid and maleylacetone but shows significantly elevated activity with (+)-2-bromo-3-(4-nitrophenyl)propanoic acid as a substrate. This elevated activity appears to be driven by a high turnover number. The diminished activity with maleylacetone results from a low turnover number
C174A
-
mutant displays significant decrease in 1-chloro-2,4-dinitrobenzene activity
C32Y
naturally occuring mutation at the primary active site residue, the rare C32Y substitution is identified in Europeans and appears to degrade rapidly. This variant does not catalyze the typical thioltransferase and reductase reactions that are a feature of the Omega class GSTs
C47A/C101A
mutant shows 41% decrease in the specific activity towards 1-chloro-2,4-dinitrobenzene compared to the His-tagged wild type enzyme
C47S/C101S
C78A
-
mutant displays significant decrease in 1-chloro-2,4-dinitrobenzene activity
C87A/C115A/C174A/M212C
-
site-directed mutagensis of isozyme GST M2-2, mutation of the catalytic site residue M212 and of all cysteines, the mutant shows altered substrate specificity compared to the wild-type isozyme. C87A/C115A/C174A/M212C, which serves as the parental enzyme for the alkylated variants, is more active than mutant C87A/C115A/C174A with 1-chloro-2,4-dinitrobenzene, cyanoDMNG, and aminochrome but shows only half of the NPG activity. Effects of alkylation of the C87A/C115A/C174A/M212C mutant on the substrate selectivity profile, overview
C88A
-
mutant displays significant decrease in 1-chloro-2,4-dinitrobenzene activity
D141N
site-directed mutagenesis of isozyme GST T1-1, the mutant enzyme behaves similarly to the wild-type enzyme, in terms of expression level and specific activity. The mutant activity with ethidium bromide is highly reduced compared to the wild-type enzyme
D201A
-
site-directed mutagenesis, G-site mutation, the mutant shows reduced activity compared to the wild-type enzyme
D43N
naturally occuring mutation, the mutant is expressed at low levels causing GSTT1 deficiency
D69A
-
site-directed mutagenesis, G-site mutation, the mutant shows reduced activity compared to the wild-type enzyme
D69T
-
site-directed mutagenesis, G-site mutation, the mutant shows reduced activity compared to the wild-type enzyme
D90N
greatly decreased specific activity, shows no appreciable changes in Km for 1-chloro-2,4-dinitrobenzene and has similar circular dichroism spectra to that of wild type enzyme, the dimer-monomer equilibrium is shifted toward monomer
D94N
greatly decreased specific activity, shows no appreciable changes in Km for 1-chloro-2,4-dinitrobenzene and has similar circular dichroism spectra to that of wild type enzyme, the dimer-monomer equilibrium is shifted toward monomer
delE155
naturally occuring mutation, the polymorphic deletion of E155, from the deletion of AGG from the 5' splice donor site of exon 4, occurs at a low frequency in most populations and is strongly linked to K208 in Europeans and to E208 in Chinese individuals. Although active enzyme can be expressed in Escherichia coli, the delE155 enzyme appears to be unstable in vivo. T47D cells that are hemizygous for the GSTO1delE155 allele are completely deficient in GSTO1-1 activity. Variable protein expression in platelets found evidence that the delE155 enzyme is present in platelets obtained from subjects that are heterozygous for the GSTO1delE155, K208 allele
E173K
site-directed mutagenesis of isozyme GST T1-1, the mutant shows reduced expression levels and enzyme activity with all substrates compared to the wild-type enzyme. The mutant is not active with ethidium bromide
E208K
naturally occuring mutation, the single E208K substitution alone, created independently of the E155 deletion, does not have a significant impact on activity. Variable protein expression in platelets found evidence that the delE155 enzyme is present in platelets obtained from subjects that are heterozygous for the GSTO1delE155, K208 allele
F83A
-
site-directed mutagenesis, H-site mutation, the mutant shows increased activity compared to the wild-type enzyme
F83W
-
site-directed mutagenesis, H-site mutation, the mutant shows increased activity compared to the wild-type enzyme
F87A
-
site-directed mutagenesis, H-site mutation, the mutant shows increased activity compared to the wild-type enzyme
F87W
-
site-directed mutagenesis, H-site mutation, the mutant shows increased activity compared to the wild-type enzyme
G112C
-
mutant displays as high catalytic activity as wild type GST M1-1
G147W
the natural polymorphism occurs in a rare variant in Chinese individual
G147W/V224I
site-directed mutagenesis, the double mutation results in a gain of function with a three fold increase in the specific activity with 1-chloro-2,4-dinitrobenzene as a substrate. This increase in activity appears to result from a decrease in the Km GSH and a large increase in the catalytic efficiency of the enzyme
I104V
I104V/A113V
I10A/G112C
-
mutant displays significant decrease in 1-chloro-2,4-dinitrobenzene activity
I10C
-
mutant displays significant decrease in 1-chloro-2,4-dinitrobenzene activity
I44A
-
site-directed mutagenesis, H-site mutation, the mutant shows reduced activity compared to the wild-type enzyme
I71V
site-directed mutagensis, structure analysis
II71A
site-directed mutagensis, structure analysis
K62A
-
site-directed mutagenesis, G-site mutation, the mutant shows reduced activity compared to the wild-type enzyme
K62E
-
site-directed mutagenesis, G-site mutation, the mutant shows reduced activity compared to the wild-type enzyme
L158I
naturally occuring mutation, the substitution is rare and may generate unstable protein
L15A
-
site-directed mutagenesis, H-site mutation, the mutant shows reduced activity compared to the wild-type enzyme
L183A
-
site-directed mutagenesis, G-site mutation, the mutant shows reduced activity compared to the wild-type enzyme
L58A
-
site-directed mutagenesis, H-site mutation, the mutant shows reduced activity compared to the wild-type enzyme
L88A
-
site-directed mutagenesis, H-site mutation, the mutant shows reduced activity compared to the wild-type enzyme
L92A
-
site-directed mutagenesis, H-site mutation, inactive mutant
M212C
-
site-directed mutagensis of isozyme GST M2-2, mutation of the catalytic site residue M212. Additionall chemical modifications at mutant Cys212, e.g. by attachment of alkyl chains, alter the substrate specificity and activity of the mutant enzyme with alternative substrates, effects of alkylation of the C87A/C115A/C174A/M212C mutant on the substrate selectivity profile, overview
M66A
-
site-directed mutagenesis, H-site mutation, inactive mutant
M91A
-
site-directed mutagenesis, H-site mutation, the mutant shows increased activity compared to the wild-type enzyme
M91K
-
site-directed mutagenesis, H-site mutation, the mutant shows increased activity compared to the wild-type enzyme
N142D
naturally occuring mutation, the N142D substitution is the most frequent in all populations studied so far and does not appear to influence catalytic activity or stability
N53A
-
site-directed mutagenesis, G-site mutation, the mutant shows reduced activity compared to the wild-type enzyme
P17A
-
site-directed mutagenesis, H-site mutation, the mutant shows increased activity compared to the wild-type enzyme
P55A
-
site-directed mutagenesis, H-site mutation, the mutant shows increased activity compared to the wild-type enzyme
R15L
site-directed mutagenesis, the mutation substantially diminishes the 1-chloro-2,4-dinitrobenzene-GSH conjugating activity of the enzyme, it has little effect on protein structure and stability
R175A
-
mutation results in a significant lowering of the turnover number for (+)-2-bromo-3-(4-nitrophenyl)propanoic acid and maleylacetone, elevated KM-value for maleylacetone
R175K
-
mutation results in a significant lowering of the turnover number for (+)-2-bromo-3-(4-nitrophenyl)propanoic acid and maleylacetone
R202A
-
site-directed mutagenesis, G-site mutation, the mutant shows reduced activity compared to the wild-type enzyme
R70Q
greatly decreased specific activity, shows no appreciable changes in Km for 1-chloro-2,4-dinitrobenzene and has similar circular dichroism spectra to that of wild type enzyme, the dimer-monomer equilibrium is shifted toward monomer
R74Q
greatly decreased specific activity, shows no appreciable changes in Km for 1-chloro-2,4-dinitrobenzene and has similar circular dichroism spectra to that of wild type enzyme, the dimer-monomer equilibrium is shifted toward monomer
S112T
naturally occuring polymorphism, recombinant enzyme containing the S110 allele has elevated activity towards 4-nitrophenylacetate and azathioprene and lower activity with 1-chloro-2,4-dinitrobenzene and organic hydroperoxides compared to the wild-type. The T112 substitution causes a reduction in levels of GSTA2-2 to around 25% of those associated with the other haplotypes
S14A
-
inactive mutant enzyme
S15A
-
mutant enzyme shows low isomerase activity with maleylacetone as a substrate (about 15% of wild-type) and low activity with chlorofluoroacetic acid, it shows elevated activity with (+)-2-bromo-3-(4-nitrophenyl)propanoic acid as the substrate
S16A
-
site-directed mutagenesis, G-site mutation, the mutant shows reduced activity compared to the wild-type enzyme
S19A
-
site-directed mutagenesis, G-site mutation, the mutant shows reduced activity compared to the wild-type enzyme
S200A
-
site-directed mutagenesis, G-site mutation, the mutant shows reduced activity compared to the wild-type enzyme
T104P
the GSTT12B allele results from the relatively rare T104P substitution in Scandinavian individuals, and appears to destabilize the protein and result in GSTT1-1 deficiency
T65M
naturally occuring mutation, the mutant is expressed at low levels causing GSTT1 deficiency
T67A
increased specific activity
T68E
-
site-directed mutagenesis, crystal structure comparison with the wild-type isozyme GST-A1-1, overview
V169
naturally occuring mutation, the mutant is expressed at low levels causing GSTT1 deficiency
V224I
a naturally occuring polymorphism common in African, Asian and European individuals
V41I
naturally occuring mutation, catalytic activity of the V41I substitution is not evaluated but the expressed protein appears to be stable.
W126A
-
site-directed mutagenesis, H-site mutation, the mutant shows increased activity compared to the wild-type enzyme
W234K
-
site-directed mutagenesis, isozyme GST T1-1, the mutant shows altered substrate specificity compared to the wild-type enzyme
W234R
Y108A
-
mutant enzyme shows 58% of the wild-type activity with 1,2-dichloro-4-nitrobenzene as substrate and 37% of the wild-type activity with 1,2-epoxy-3-(p-nitrophenoxy)propane, 2% of the wild-type GSH peroxidase activity towards cumene hydroperoxide and 163% of the wild-type steroid isomerase activity towards DELTA5-androstene-3,17-dione
Y108F
-
mutant enzyme is as active as wild-type enzyme with 1,2-dichloro-4-nitrobenzene as substrate and shows 7% of the wild-type activity with 1,2-epoxy-3-(p-nitrophenoxy)propane, 77% of the wild-type GSH peroxidase activity towards cumene hydroperoxide and 149% of the wild-type steroid isomerase activity towards DELTA5-androstene-3,17-dione. Mutation results in an approximately 3fold decrease in the I50 value of S-methyl-GSH
Y108W
-
mutant enzyme shows 215% of the wild-type activity with 1,2-dichloro-4-nitrobenzene as substrate and 35% of the wild-type activity with 1,2-epoxy-3-(p-nitrophenoxy)propane, 16% of the wild-type GSH peroxidase activity towards cumene hydroperoxide and 36% of the wild-type steroid isomerase activity towards DELTA5-androstene-3,17-dione. Mutation results in an approximately 3fold decrease in the I50 value of S-methyl-GSH. Lower heat stability than wild-type enzyme
Y18A
-
site-directed mutagenesis, G-site mutation, inactive mutant
Y18F
-
site-directed mutagenesis, G-site mutation, the mutant shows reduced activity compared to the wild-type enzyme
Y18H
-
site-directed mutagenesis, G-site mutation, inactive mutant
Y18L
-
site-directed mutagenesis, G-site mutation, inactive mutant
Y7F
mutant shows 99% decrease in the specific activity towards 1-chloro-2,4-dinitrobenzene compared to the His-tagged wild type enzyme
Y9F
-
site-directed mutagenesis of isozyme GSTA4-4
S9A
-
decreased kcat
Y113F
-
increased kcat
T13A
-
reduced hydrogen bonding strength to the glutathione's sulfur and decreased stability of the thiolate anion
T13V
-
reduced hydrogen bonding strength to the glutathione's sulfur and decreased stability of the thiolate anion
C14A
site-directed mutagenesis
C14A/C169A
site-directed mutagenesis
C14A/C47A
site-directed mutagenesis
C169A
site-directed mutagenesis
C47A
site-directed mutagenesis
C47A/C169A
site-directed mutagenesis
R234W
-
site-directed mutagenesis
F108G
site-directed mutagenesis, the mutant shows reduced affinity and catalytic activity to both GSH and the electrophilic co-substrate, 1-chloro-2,4-dinitrobenzene, compared to the wild-type enzyme
R113A
site-directed mutagensis, the mutant shows activity slightly reduced affinity and catalytic activity to both GSH and the electrophilic co-substrate, 1-chloro-2,4-dinitrobenzene, compared to the wild-type enzyme
E66A
the mutant shows reduced activity compared to the wild type enzyme
F119A
the mutant shows reduced activity compared to the wild type enzyme
H52A
the mutant shows reduced activity compared to the wild type enzyme
R68A
the mutant shows reduced activity compared to the wild type enzyme
S11A
the mutant shows reduced activity compared to the wild type enzyme
S67A
the mutant shows reduced activity compared to the wild type enzyme
V54A
the mutant shows reduced activity compared to the wild type enzyme
N14A
Q2G4B4; Q2G4B5
the mutant of subunit A has a kcat value about 20fold lower and a Km value about 12.5fold higher than that of the wild type enzyme
S14A
Q2G4B4; Q2G4B5
the mutant of subunit B has the same kcat and Km values as the wild type enzyme
S14A/S15A
Q2G4B4; Q2G4B5
the double mutant has a kcat value similar to that of the wild type enzyme and a Km value that is 5-6fold higher than that of the wild type enzyme
S15A
Q2G4B4; Q2G4B5
the mutant of subunit A has a kcat value similar to that of the wild type enzyme and a Km value that is 5-6fold higher than that of the wild type enzyme
N14A
-
the mutant of subunit A has a kcat value about 20fold lower and a Km value about 12.5fold higher than that of the wild type enzyme
-
S14A
-
the mutant of subunit B has the same kcat and Km values as the wild type enzyme
-
S14A/S15A
-
the double mutant has a kcat value similar to that of the wild type enzyme and a Km value that is 5-6fold higher than that of the wild type enzyme
-
S15A
-
the mutant of subunit A has a kcat value similar to that of the wild type enzyme and a Km value that is 5-6fold higher than that of the wild type enzyme
-
E68A
the mutant retains activity toward 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole, 1-chloro-2,4-dinitrobenzene and 4-nitrobenzyl chloride, but its activities drop significantly compared to the wild type enzyme
F116A
the mutant shows reduced catalytic efficiency toward glutathione and 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole as compared to the wild type enzyme
F162A
the mutant shows reduced catalytic efficiency toward glutathione and 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole as compared to the wild type enzyme
K42A
the mutant shows 10% of wild type activity
L112A
the mutant shows reduced catalytic efficiency toward glutathione and increased catalytic efficiency toward 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole as compared to the wild type enzyme
M17A
the mutant shows reduced catalytic efficiency toward glutathione and 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole as compared to the wild type enzyme
N109A
the mutant shows reduced catalytic efficiency toward glutathione and 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole as compared to the wild type enzyme
S15A
inactive
S69A
the mutant loses activity to 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole while it retains 31% of the activity toward 1-chloro-2,4-dinitrobenzene and 7-8% of the activity toward 4-nitrobenzyl chloride, respectively, compared with the wild type enzyme
V56A
the mutant loses activity to 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole while it retains 21% of the activity toward 1-chloro-2,4-dinitrobenzene and 7-8% of the activity toward 4-nitrobenzyl chloride, respectively, compared with the wild type enzyme
W161A
the mutant shows reduced catalytic efficiency toward glutathione and increased catalytic efficiency toward 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole as compared to the wild type enzyme
Y113A
the mutant shows reduced catalytic efficiency toward glutathione and 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole as compared to the wild type enzyme
S22A
site-directed mutagenesis
S22C
site-directed mutagenesis
E66A
-
activity with 1-chloro-2,4-dinitrobenzene is 18.4fold lower than wild-type activity, activity with ethacrynic acid is 1.25fold higher than wild-type activity, activity with 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole is 3fold lower than wild-type activity, no activity with 4-nitrophenyl acetate. More thermolabile than wild-type enzyme. Refolding after denaturation is higher than the refolding of the wild-type enzyme
I54A
-
activity with 1-chloro-2,4-dinitrobenzene is 2fold lower than wild-type activity, activity with ethacrynic acid is 3.5fold higher than wild-type activity, activity with 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole is 2.8fold higher than wild-type activity, no activity with 4-nitrophenyl acetate. More thermolabile than wild-type enzyme. Refolding after denaturation is lower than the refolding of the wild-type enzyme
K40A
-
activity with 1-chloro-2,4-dinitrobenzene is 18fold lower than wild-type activity, activity with ethacrynic acid is 1.2fold lower than wild-type activity, activity with 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole is nearly identical to wild-type activity, no activity with 4-nitrophenyl acetate. More thermolabile than wild-type enzyme. Refolding after denaturation is lower than the refolding of the wild-type enzyme
S13A
mutant enzyme shows no significant GST activity with 1-chloro-2,3-dinitrobenzene or with 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole
S67A
-
activity with 1-chloro-2,4-dinitrobenzene is fold 21.6fold lower than wild-type activity, activity with ethacrynic acid is 1.13fold lower than wild-type activity, activity with 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole is 3.9fold lower than wild-type activity, no activity with 4-nitrophenyl acetate. More thermolabile than wild-type enzyme. Refolding after denaturation is higher than the refolding of the wild-type enzyme
C101A
-
site-directed mutagenesis, the mutant shows unaltered ligand binding compared to the wild-type enzyme
C86A
-
site-directed mutagenesis, the mutant shows unaltered ligand binding compared to the wild-type enzyme
K15E
-
site-directed mutagenesis, the mutant shows altered ligand binding compared to the wild-type enzyme
Q71E
-
site-directed mutagenesis, the mutant shows altered ligand binding compared to the wild-type enzyme
Y211F
-
site-directed mutagenesis, the mutant shows unaltered ligand binding compared to the wild-type enzyme
Y9F
-
site-directed mutagenesis, the mutant shows unaltered ligand binding compared to the wild-type enzyme
F113A
-
site-directed mutagenesis of the H-site residue, the mutant shows altered substrate specificity and activity compared to the wild-type enzyme
G8A
-
site-directed mutagenesis of the H-site residue
H167A
-
site-directed mutagenesis of the H-site residue, the mutant shows altered substrate specificity and activity compared to the wild-type enzyme
S110A
-
site-directed mutagenesis of the H-site residue, the mutant shows altered substrate specificity and activity compared to the wild-type enzyme
W164A
-
site-directed mutagenesis of the H-site residue the mutant shows altered substrate specificity and activity compared to the wild-type enzyme
D97K
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
D97R
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
E100K
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
E100R
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
E80Q
7% residual activity compared to the wild type enzyme
H75Q
34% residual activity compared to the wild type enzyme
N101D
-
site-directed mutagenesis, the mutant shows increased activity compared to the wild-type enzyme
N101K
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
R113K
5% residual activity compared to the wild type enzyme
R131M
-
mutant enzyme shows 60% of wild-type activity with 1-chloro-2,4-dinitrobenzene as substrate
R131Q
-
mutant enzyme shows 50% of wild-type activity with 1-chloro-2,4-dinitrobenzene as substrate
R131W
-
mutant enzyme shows 24% of wild-type activity with 1-chloro-2,4-dinitrobenzene as substrate
R15Q
-
mutant enzyme shows 0.02% of wild-type activity with 1-chloro-2,4-dinitrobenzene as substrate
R63A
30% increased activity compared to the wild type enzyme
R72A
42% residual activity compared to the wild type enzyme
R73Q
57% residual activity compared to the wild type enzyme
R77E
-
site-directed mutagenesis, the mutant shows increased activity compared to the wild-type enzyme
R77Q
-
site-directed mutagenesis, the mutant shows increased activity compared to the wild-type enzyme
S30A
400% increased activity compared to the wild type enzyme
T64V
280% increased activity compared to the wild type enzyme
Y9F
-
mutant enzyme shows 0.8% of wild-type activity with 1-chloro-2,4-dinitrobenzene as substrate. 4.3fold increase in KM-value for GSH compared to wild-type value, 1.3fold decrease in KM-value for 1-chloro-2,3-dinitrobenzene
Y9T
-
mutant enzyme shows 0.06% of wild-type activity with 1-chloro-2,4-dinitrobenzene as substrate
A122C
-
the single-site mutation A122C and N124A/V (but not N124S/Y/C) restores the GST activity of Ure2p protein toward 1-chloro-2,4-dinitrobenzene, while causing a substantial reduction in glutathione peroxidase activity
N124V
-
the single-site mutation A122C and N124A/V (but not N124S/Y/C) restores the GST activity of Ure2p protein toward 1-chloro-2,4-dinitrobenzene, while causing a substantial reduction in glutathione peroxidase activity
I55T
the mutant of isoform GSTU6 shows strongly decreased activity compared to the wild type enzyme
T53I
the mutant of isoform GSTU7 shows strongly increased activity compared to the wild type enzyme
T53V
the mutant of isoform GSTU7 shows strongly increased activity compared to the wild type enzyme
K44A
-
the mutant shows 95.9% binding affinity for GSH compared to the wild type enzyme
K44A/W40F
-
the mutant shows 95.2% binding affinity for GSH compared to the wild type enzyme
K44A/W40G
-
the mutant shows 65.7% binding affinity for GSH compared to the wild type enzyme
K44G
-
the mutant shows 97% binding affinity for GSH compared to the wild type enzyme
K44G/W40A/R41A
-
the mutant shows 49.3% binding affinity for GSH compared to the wild type enzyme
K44S
-
the mutant shows 95.6% binding affinity for GSH compared to the wild type enzyme
K44S/W40F/R41A
-
the mutant shows 66.2% binding affinity for GSH compared to the wild type enzyme
R41A
-
the mutant shows 97.5% binding affinity for GSH compared to the wild type enzyme
R41H
-
the mutant shows 99.55% binding affinity for GSH compared to the wild type enzyme
W40A
-
the mutant shows 89.7% binding affinity for GSH compared to the wild type enzyme
W40F
-
the mutant shows 96.7% binding affinity for GSH compared to the wild type enzyme
W40G
-
the mutant shows 81.1% binding affinity for GSH compared to the wild type enzyme
I118F
Q53A
site-directed mutagenesis, the mutant of isozyme GST I exhibits 9.2fold higher inhibition potency for the insecticide malathion compared to the wild-type enzyme, mutant immobilization by crosslinking with glutaraldehyde for formation of a malathion biosensor, overview
W12P
-
turnover number with 1-chloro-2,4-dinitrobenzoate is 7.6% of the wild-type value, the ratio of turnover number to KM-value is 3.7% of the wild-type value, turnover number with ethacrynic acid is 9.5% of the wild-type value
additional information