1.11.1.21: catalase-peroxidase

the mutant shows unchanged catalase and peroxidase activities compared to the wild type enzyme

A143V

the mutant shows unchanged catalase and peroxidase activities compared to the wild type enzyme

A290Q

the mutant shows unchanged catalase and peroxidase activities compared to the wild type enzyme

A290Y

the mutant shows unchanged catalase and peroxidase activities compared to the wild type enzyme

D141A

5 entries

D141A/R108A

the reaction with peroxyacetic acid is clearly slower than for mutant D141A

715665

D141E

3 entries

D141N

E242Q

the mutant shows unchanged catalase and peroxidase activities compared to the wild type enzyme

H112A

the mutant shows 0.02% of wild type catalase activity and 2.3% of wild type peroxidase activity

H112N

the mutant shows 0.05% of wild type catalase activity and 2.3% of wild type peroxidase activity

L209D

the mutant shows unchanged catalase and peroxidase activities compared to the wild type enzyme

L236D

the mutant shows unchanged catalase and peroxidase activities compared to the wild type enzyme

M264A

the mutant shows 0.15% of wild type catalase activity and 160% of wild type peroxidase activity

M264L

the mutant shows 0.02% of wild type catalase activity and 140% of wild type peroxidase activity

Q233E

the mutant shows unchanged catalase and peroxidase activities compared to the wild type enzyme

R108A

4 entries

R108A/D141A

R108A/W111F

the mutant shows stronglydecreased catalase and peroxidase activities

716867

R108A/W111F/D141A

the mutant shows strongly decreased catalase and peroxidase activities

716867

R108K

R426A

the mutant shows 4.3% of wild type catalase activity and 99% of wild type peroxidase activity

R426K

the mutant shows 70% of wild type catalase activity and 97% of wild type peroxidase activity

S324T

the mutant shows 109% of wild type catalase activity and 94% of wild type peroxidase activity

W111F

W309F

the mutant shows unchanged catalase and peroxidase activities compared to the wild type enzyme

W330F

the mutant exhibits slightly reduced catalase- and peroxidase-specific activities but a faster peroxidase turnover rate compared to the wild type enzyme

715665

Y238A

the mutant shows 0.05% of wild type catalase activity and 140% of wild type peroxidase activity

Y238F

the mutant shows 0.15% of wild type catalase activity and 64% of wild type peroxidase activity

A143Q

the mutant shows unchanged catalase and peroxidase activities compared to the wild type enzyme

A143V

the mutant shows unchanged catalase and peroxidase activities compared to the wild type enzyme

D141A

the mutant shows reduced catalase and peroxidase activities compared to the wild type enzyme

E242Q

the mutant shows unchanged catalase and peroxidase activities compared to the wild type enzyme

W309F

the mutant shows unchanged catalase and peroxidase activities compared to the wild type enzyme

DELTA200-214

mutation eliminates catalase activity, but variant is substantially more active as peroxidase

725649

DELTA209-228

variant is substantially more active as peroxidase

725649

DELTAL193-N228

mutant lacking Large Loop1, mutation eliminates catalase activity, but variant is substantially more active as peroxidase

H106C

H106Y

H257Y

the mutant shows 0.05% of wild type catalase activity and 1.8% of wild type peroxidase activity

H267Y

the peroxidatic-to-catalatic ratio of the mutant is increased 36fold, the heme content of the mutant is reduced relative to the wild type enzyme

R102C

R102K

R102L

W105F

W105L

Y111A

the mutation leads to a 5fold reduction in the apparent kcat for catalase activity and an 8fold decrease in the apparent second-order rate constant. For peroxidase activity, the H2O2- and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)-dependent peroxidatic apparent kcat are reduced by 66% and 40%, respectively. Preparations of this variant yield a mixture of high- and low-spin heme states, thus creating the appearance of a transition between wild type (high-spin) and C-terminal lacking (low-spin) KatG

688196

Y226F

mutation eliminates catalase activity, but variant is substantially more active as peroxidase

725649

H106Y

the peroxidatic-to-catalatic ratio of the mutant is increased 321fold, the heme content of the mutant is reduced relative to the wild type enzyme

R102C

the peroxidatic-to-catalatic ratio of the mutant is increased 18fold, the heme content of the mutant is reduced relative to the wild type enzyme

R102K

the peroxidatic-to-catalatic ratio of the mutant is increased 7fold, the heme content of the mutant is reduced relative to the wild type enzyme

R102L

the peroxidatic-to-catalatic ratio of the mutant is increased 13fold, the heme content of the mutant is reduced relative to the wild type enzyme

W105F

the peroxidatic-to-catalatic ratio of the mutant is increased 2800fold, the heme content of the mutant is reduced relative to the wild type enzyme

A110V

A139P

site-directed mutagenesis, 76% decreased activity with and activation of isoniazid compared to the wild-type enzyme

A350T

the catalase and peroxidase activities and isoniazid sensitivity is similar to the wild type enzyme

D137S

in the presence of H2O2, the adduct radical formed from covalently linked side chains of conserved amino acids Met255, Tyr229, and Trp107 is formed normally, but mutant is defective in forming dioxyheme and lacks catalase activity. Mutant exhibits a coincidence between adduct radical persistence and H2O2 consumption as a function of time, and enhanced subunit oligomerization during turnover

725495

D381G

the mutant shows no catalase activity

D387G

naturally occuring mutation in KatG which causes INH resistance to a very high level

D735A

site-directed mutagenesis, 73% decreased activity with and activation of isoniazid compared to the wild-type enzyme

E291A

the mutant shows 89% peroxidase activity and 139% catalase activity compared to the wild type enzyme

E291K

the mutant shows 200% peroxidase activity and 79% catalase activity compared to the wild type enzyme

E291K/E292A

the mutant shows 222% peroxidase activity and 102% catalase activity compared to the wild type enzyme

E695A

only subtle variations in spectroscopic and catalytic properties of the enzyme, substantial decrease in the rate and extent of KatG N-terminal domain reactivation

E695A/Y697A

substantial increase in hexa-coordinate low-spin heme and diminished enzyme activity, complete loss of the capacity for the reactivation of the N-terminal domain

G273C

site-directed mutagenesis near the heme center, the mutation causes a decrease in the the volume of the catalytic center

G316S

naturally occuring mutation in KatG which does not cause INH resistance

G421S

site-directed mutagenesis, of amino acids alteration in the mutant, substitution of T354I and G421S create significant instability in the adduct triad complex (Trp107-Tyr229-Met255), a part of the active site of the catalase-peroxidase enzyme in the model structure analysis

765229

H108E

isoniazid-resistant clinical mutant

714115

H108L

H108Q

H270Q

the mutant shows no catalase activity

H52L

isoniazid-resistant clinical mutant

714115

H97R/L200Q

site-directed mutagenesis near the heme center, the mutation causes a decrease in the the volume of the catalytic center

I290A

the mutant shows 31% peroxidase activity and 93% catalase activity compared to the wild type enzyme

I290A/Q293A

the mutant shows 56% peroxidase activity and 64% catalase activity compared to the wild type enzyme

I290V

the mutant shows 35% peroxidase activity and 67% catalase activity compared to the wild type enzyme

I290V/Q293V

the mutant shows 44% peroxidase activity and 47% catalase activity compared to the wild type enzyme

L148R

the mutant shows no catalase activity

L499M

naturally occuring mutation in KatG which does not cause INH resistance

L587M

L587P

naturally occuring mutation in KatG which does not cause INH resistance

L619P

site-directed mutagenesis, no remaining activity with and activation of isoniazid

L634F

site-directed mutagenesis, 36% decreased activity with and activation of isoniazid compared to the wild-type enzyme

L690A/R691A

substantial increase in hexa-coordinate low-spin heme and diminished enzyme activity, complete loss of the capacity for the reactivation of the N-terminal domain

L690A/R691A/E695A/Y697A

substantial increase in hexa-coordinate low-spin heme and diminished enzyme activity, complete loss of the capacity for the reactivation of the N-terminal domain

M255A

the mutant exhibits severely reduced catalase activity compared to the wild type enzyme

698985

N138S

the KatG level of the mutant is 30% of wild type level, the mutant shows a 90% reduction in peroxidase activity

N238S

the catalytic efficiency (Kcat/KM) of the mutant decreases to 41 and 52% for catalase and peroxidase, respectively, compared to the wild type enzyme

743881

Q293A

the mutant shows 59% peroxidase activity and 102% catalase activity compared to the wild type enzyme

Q293E

the mutant shows 62% peroxidase activity and 80% catalase activity compared to the wild type enzyme

Q293V

the mutant shows 25% peroxidase activity and 44% catalase activity compared to the wild type enzyme

R104L

R385W

naturally occuring mutation in KatG which causes INH resistance to a very high level

R418L

R463G

the catalase and peroxidase activities and isoniazid sensitivity is similar to the wild type enzyme

R463L

5 entries

R691A

only subtle variations in spectroscopic and catalytic properties of the enzyme, substantial decrease in the rate and extent of KatG N-terminal domain reactivation

S140N

the catalase and peroxidase activities and isoniazid sensitivity is similar to the wild type enzyme

S140N/A350T/R463L/R463G/L587M

the mutant katG has catalase-peroxidase activities higher than wild-type katG and exhibits INH sensitivity

S315G

S315I

S315N

S315R

S315T

T275P

T354I

765229

T354I/G421S/R463L/V721M

naturally occuring mutation. The Mycobacterium tubeculsosis clinical isolate R2 contains four mutations, i.e. C1061T, G1261A, G1388T, G2161A, which correspond to the amino acid substitutions T354I, G421S, R463L, and V721M, respectively, leading to high level isoniazid (INH) resistance. The mutant enzyme showed 86.5% of catalase and 45% of peroxidase activities in comparison to the wild-type enzyme. Substitutions of T354I and G421S in mutant katG R2 create significant instability in the adduct triad complex (Trp107-Tyr229-Met255), a part of the active site of the catalase-peroxidase enzyme in the model structure analysis. Mutant phenotype and stability, overview

765229

W107F

W107F/W321F

the mutant shows decreased catalase catalytic efficiency compared to the wild type enzyme

714795

W107R

site-directed mutagenesis of the catalytic residue, the mutant displays only one heme bound per homodimer of protein. The heme is absent from protomer A and displays significant structural disorder in the vicinity of the heme binding site. Several areas surrounding the heme pocket are difficult to model in protomer A, either displaying minimal or fragmented density. The mutant C-terminal domain of both protomers remains similar to wild-type KatG. The mutant's Arg residue results in disruption of the covalently linked catalytic triad. The loop containing Tyr229, which is part of the MYW catalytic triad is disordered in both protomers, presumably as a consequence of the mutation

765846

W321F

W321G

the KatG level of the mutant is 40% of wild type level, the mutant shows a 70% reduction in peroxidase and catalase activities

Y229F

Y697A

only subtle variations in spectroscopic and catalytic properties of the enzyme, substantial decrease in the rate and extent of KatG N-terminal domain reactivation

A110V

naturally occuring mutation in KatG which does not cause INH resistance

G421S

S140N/A350T/R463L/R463G/L587M

the mutant katG has catalase-peroxidase activities higher than wild-type katG and exhibits INH sensitivity

S315G

site-directed mutagenesis, modelling and docking and interaction analysis with isoniazid, comparison to wild-type

S315I

site-directed mutagenesis, modelling and docking and interaction analysis with isoniazid, comparison to wild-type

S315N

S315R

site-directed mutagenesis, modelling and docking and interaction analysis with isoniazid, comparison to wild-type

S315T

4 entries

T275P

site-directed mutagenesis of the residue from the loop close to the heme binding site. The structure of mutant T275P displays significant areas of disorder compared with the wild-type KatG. Several loops surrounding the heme pocket contain little or no density in either protomer A or B. These disordered regions are identical to those in protomer A of the W107R variant. The loop containing the Thr275 residue (residues 274-329) displays no density and therefore cannot be modeled

T354I/G421S/R463L/V721M

W107R

A110V

naturally occuring mutation in KatG which does not cause INH resistance

G421S

L148R

the mutant shows no catalase activity

L587M

the mutant has wild type-like strong catalase and peroxidase activities

M255A

the mutant exhibits severely reduced catalase activity compared to the wild type enzyme

N238S

the catalytic efficiency (Kcat/KM) of the mutant decreases to 41 and 52% for catalase and peroxidase, respectively, compared to the wild type enzyme

R104L

R418L

the mutant shows 0.6% of wild type catalase activity and 192% of wild type peroxidase activity

R463L

S140N

the catalase and peroxidase activities and isoniazid sensitivity is similar to the wild type enzyme

S140N/A350T/R463L/R463G/L587M

the mutant katG has catalase-peroxidase activities higher than wild-type katG and exhibits INH sensitivity

S315G

site-directed mutagenesis, modelling and docking and interaction analysis with isoniazid, comparison to wild-type

S315I

site-directed mutagenesis, modelling and docking and interaction analysis with isoniazid, comparison to wild-type

S315N

S315R

site-directed mutagenesis, modelling and docking and interaction analysis with isoniazid, comparison to wild-type

S315T

7 entries

T275P

T354I/G421S/R463L/V721M

W107F

the mutant exhibits severely reduced catalase activity yet normal peroxidase activity and contains more abundant 6-coordinate heme in high spin and low spin forms compared to the wild type enzyme

W107R

W321F

the mutant shows 38% of wild type catalase activity and 18% of wild type peroxidase activity

Y229F

C26A/C74A

kinetic constants similar to wild-type, decrease in melting temperature due to loss of disulfide bridge

C55A

kinetic constants similar to wild-type, decrease in melting temperature due to loss of disulfide bridge

C55A/C74A

kinetic constants similar to wild-type, decrease in melting temperature due to loss of disulfide bridge

C74A

kinetic constants similar to wild-type, decrease in melting temperature due to loss of disulfide bridge

R461A

C26A/C74A

Pyricularia grisea ATCC MYA-4617

kinetic constants similar to wild-type, decrease in melting temperature due to loss of disulfide bridge

C55A

Pyricularia grisea ATCC MYA-4617

kinetic constants similar to wild-type, decrease in melting temperature due to loss of disulfide bridge

C55A/C74A

Pyricularia grisea ATCC MYA-4617

kinetic constants similar to wild-type, decrease in melting temperature due to loss of disulfide bridge

C74A

Pyricularia grisea ATCC MYA-4617

kinetic constants similar to wild-type, decrease in melting temperature due to loss of disulfide bridge

S308T

D152N

the mutant shows 2.7% of wild type catalase activity and 234% of wild type peroxidase activity

D152S

the mutant shows 5.7% of wild type catalase activity and 237% of wild type peroxidase activity

D152W

the mutant shows 0.6% of wild type catalase activity and 672% of wild type peroxidase activity

D402E

the mutant shows 0.6% of wild type catalase activity and 65% of wild type peroxidase activity

D402N

the mutant shows 0.5% of wild type catalase activity and 56% of wild type peroxidase activity

E253D

the mutant shows 42% of wild type catalase activity and 280% of wild type peroxidase activity

E253Q

the mutant shows 25% of wild type catalase activity and 96% of wild type peroxidase activity

H123E

the mutant shows 0.03% of wild type catalase activity and 13% of wild type peroxidase activity

H123Q

the mutant shows 0.02% of wild type catalase activity and 7.4% of wild type peroxidase activity

H290Q

the mutant shows 0.09% of wild type catalase activity and 5.6% of wild type peroxidase activity

I248F

the mutant shows 12% of wild type catalase activity and 124% of wild type peroxidase activity

M275I

the mutant shows 0.6% of wild type catalase activity and 640% of wild type peroxidase activity

N153A

the mutant shows 6% of wild type catalase activity and 60% of wild type peroxidase activity

N153D

the mutant shows 17% of wild type catalase activity and 130% of wild type peroxidase activity

N251L

the mutant shows 33% of wild type catalase activity and 415% of wild type peroxidase activity

P252A

the mutant shows 110% of wild type catalase activity and 97% of wild type peroxidase activity

R119A

the mutant shows 15% of wild type catalase activity and 12% of wild type peroxidase activity

R119N

the mutant shows 0.5% of wild type catalase activity and 5% of wild type peroxidase activity

R439A

the mutant shows 4.9% of wild type catalase activity and 12% of wild type peroxidase activity

R439N

the mutant shows 3.1% of wild type catalase activity and 100% wild type peroxidase activity

S335T

the mutant shows 99% of wild type catalase activity and 103% of wild type peroxidase activity

W122A

the mutant shows no catalase activity and 100% wild type peroxidase activity

W122F

the mutant shows no catalase activity and 90% of wild type peroxidase activity

W341A

the mutant shows 0.5% of wild type catalase activity and 25% of wild type peroxidase activity

W341F

the mutant shows 42% of wild type catalase activity and 190% of wild type peroxidase activity

Y249F

the mutant shows 0.17% of wild type catalase activity and 121% of wild type peroxidase activity

D152N

the mutant shows 2.7% of wild type catalase activity and 234% of wild type peroxidase activity

D402E

the mutant shows 0.6% of wild type catalase activity and 65% of wild type peroxidase activity

D402N

the mutant shows 0.5% of wild type catalase activity and 56% of wild type peroxidase activity

H290Q

the mutant shows 0.09% of wild type catalase activity and 5.6% of wild type peroxidase activity

R119A

the mutant shows 15% of wild type catalase activity and 12% of wild type peroxidase activity

D152N

site-directed mutagenesis, 2.7% remaining catalase activity and 2-7times higher peroxidase activity compared to the wild-type enzyme, highly altered pH profile

654706

D152S

3 entries

D152W

site-directed mutagenesis, 0.6% remaining catalase activity and 2-7times higher peroxidase activity compared to the wild-type enzyme, highly altered pH profile

654706

E253Q

the mutant shows strongly reduced catalase activity

714328

H123E

mutant with very low catalase activity

715014

N153A

the mutant shows 6% of wild type catalase activity and exhibits an overall peroxidase activity similar with wild type KatG

714890

N153D

the mutant shows 16.5% of wild type catalase activity and exhibits an overall peroxidase activity similar with wild type KatG

714890

P151A

site-directed mutagenesis, slightly increased catalase activity compared to the wild-type enzyme

654706

R439A

mutant with very low catalase activity

715014

W122F

Y249F

D152N

site-directed mutagenesis, residue of the heme binding pocket distal side, mutation effect on heme structure and residue interaction, reduced catalase activity and increased peroxidase activity compared to the wild-type enzyme

D152S

D152W

site-directed mutagenesis, residue of the heme binding pocket distal side, mutation effect on heme structure and residue interaction, highly reduced catalase activity and highly increased peroxidase activity compared to the wild-type enzyme

D402E

site-directed mutagenesis, residue of the heme binding pocket proximal side, mutation effect on heme structure and residue interaction, reduced catalase and peroxidase activity compared to the wild-type enzyme

D402N

H290Q

site-directed mutagenesis, residue of the heme binding pocket proximal side, mutation effect on heme structure and residue interaction, highly reduced catalase and peroxidase activity compared to the wild-type enzyme

N153A

site-directed mutagenesis, residue of the heme binding pocket distal side, mutation effect on heme structure and residue interaction

N153D

site-directed mutagenesis, residue of the heme binding pocket distal side, mutation effect on heme structure and residue interaction

P151A

site-directed mutagenesis, residue of the heme binding pocket distal side, mutation effect on heme structure and residue interaction, slightly reduced catalase and peroxidase activity compared to the wild-type enzyme

W341A

W341F

site-directed mutagenesis, residue of the heme binding pocket proximal side, mutation effect on heme structure and residue interaction, 50% reduced catalase activity and 50% increased peroxidase activity compared to the wild-type enzyme, binds completely to NaF