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Mn2+
activates, and reactivates the metal-depleted PZase
Ni2+
activates, and facilitates the deprotonation of coordinates water molecules to generate a nucleophile that catalyzes the enzymatic reaction
Fe2+
-
the iron binding site residues are Asp49, His51, His57, and His71
Co2+
activates
Co2+
activates, and reactivates the metal-depleted PZase, and facilitates the deprotonation of coordinates water molecules to generate a nucleophile that catalyzes the enzymatic reaction
Fe2+
required, enzyme-bound
Fe2+
activates, cannot reactivate the metal-depleted PZase, but facilitates the deprotonation of coordinated water molecules to generate a nucleophile that catalyzes the enzymatic reaction
Fe2+
iron shows weak binding with the metal coordination site of the mutant proteins due to alteration in electron transfer mechanism
Fe2+
required, enzyme-bound, the metal binding site contains iron (Fe2+ ion) in coordination with one aspartate (Asp49) and three histidines residues (His51, His57, and His71)
Fe2+
required, enzyme-bound. Mutations N11K and P69T cause destabilization of the Fe2+ binding site, structure overview
Fe2+
residues D49, H51, H57, H71 comprise a metal coordinating site coordinating an Fe2+ or Zn2+ cation
Fe2+
the enzyme contains a Fe2+ ion surrounded by one aspartate and three histidines in the substrate binding cavity along with three water molecules
Zn2+
activates, and reactivates the metal-depleted PZase
Zn2+
residues D49, H51, H57, H71 comprise a metal coordinating site coordinating an Fe2+ or Zn2+ cation
additional information
Asp49, His51, His57, and His71 are the metal ion binding residues
additional information
-
Asp49, His51, His57, and His71 are the metal ion binding residues
additional information
Mn2+, Co2+, Sr2+, Ba2+, Fe3+, Mg2+, and Ca2+ cannot significantly change the activity and stability of PZase
additional information
PZase is a metalloenzyme, metal binding structure, overview. The metal coordination site of the enzyme is able to coordinate various divalent metal cofactors. Effects of metal-ion replacement on pyrazinamidase activity, quantum mechanics calculations and simulations, metal-ligand (residue) binding energy and atomic partial charges in the presence of various ions, overview. Co2+, Mn2+, and Zn2+ are able to reactivate metal-depleted PZase, while Cu2+, Fe2+, and Mg2+ cannot restore activity. The coordination of Ni2+, Co2+, or Fe2+ to PZase facilitates the deprotonation of coordinated water molecules to generate a nucleophile that catalyzes the enzymatic reaction
additional information
the substitution of iron with cobalt enhances the enzymatic activity of both wild-type and mutant PZase while zinc, magnesium and copper reduce it. Upon substitution of iron with zinc, magnesium and copper, PZase cannot function properly. Molecular level DFT based quantum mechanics computational analysis of mutant-metal substituted PZase complexes based on crystal structure PDB ID 3PL1, enzyme-metal binding analysis, overview
additional information
-
the substitution of iron with cobalt enhances the enzymatic activity of both wild-type and mutant PZase while zinc, magnesium and copper reduce it. Upon substitution of iron with zinc, magnesium and copper, PZase cannot function properly. Molecular level DFT based quantum mechanics computational analysis of mutant-metal substituted PZase complexes based on crystal structure PDB ID 3PL1, enzyme-metal binding analysis, overview
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metabolism
pyrazinamide (PZA), a derivative of nicotinamide is one of the most imperative first-line drug treatments against tuberculosis. PZA is significantly used in MDR tuberculosis in combination with isoniazid, rifampicin and ethambutol in regimens. The most potent action of the drug is against the semi-dormant bacilli in an acidic environment, which cannot be treated with most other drugs and thus helps in shortening the chemotherapy period
physiological function
pyrazinamide (PZA) is an important component of first-line anti-tuberculosis (anti-TB) drugs. The anti-TB agent is activated into an active form, pyrazinoic acid, by Mycobacterium tuberculosis (MTB) pncA gene encoding pyrazinamidase (PZase)
malfunction
analysis of mutations in pyrazinamidase and effects of the mutations at the metal coordination site and conformational changes in PZase binding cavity on the enzyme activity, quantum mechanical calculations, overview. Iron shows weak binding with the metal coordination site of the mutant proteins due to alteration in electron transfer mechanism. The binding cavity of the mutant PZase has undergone major conformational changes as the volume of pocket increased due to bulky R-chains of mutated amino acids. These conformational changes lead to weak binding of the drug at binding cavity of PZase and reduce the drug activation mechanism leading to increased drug resistance in the bacterial strains. The template structure used is the tertiary structure of pyrazinamidase from Mycobacterium tuberculosis, PDB ID 3PL1
malfunction
cumulative effect of mutations and iron substitution
malfunction
estimation of pyrazinamidase activity using a cell-free in vitro synthesis of pncA and its association with pyrazinamide susceptibility in Mycobacterium tuberculosis, mutant phenotypes, overview
malfunction
identification and multiple analyses to unveil different mechanisms of resistance of PZase mutants L19R, R140H, and E144K, overview. The native PZase protein docking score is the maximum, showing strong binding affinity in comparison with mutants. Molecular dynamics simulations explore the effect of the variants on the biological function of PZase. Hydrogen bonding, metal ion Fe2+ deviation, and fluctuation also seem to be affected because of the mutations L19R, R140H, and E144K. The mutant variants play a significant role in PZA resistance, altering the overall activity of native PZase, including metal ion Fe2+ displacement and free energy
malfunction
mechanisms of the pyrazinamide (PZA) resistance of three pyrazinamidase mutants N11K, P69T, and D126N. In general, pyrazinoic acid (PZA) resistance is caused by three genes pncA, rpsA, and panD. Among them, the pncA gene contributes 72-99% to the resistance. The binding pocket analysis shows that mutations N11K and P69T decrease the volume of the active site and hinder the correct orientation of PZA drug in the active site. Moreover, the Patchdock score is low as compared to wild-type showing the disturbance of shape complementarity between enzyme PZase and PZA drug. These mutations N11K, P69T, and D126N disturb the position of the Fe2+ ion. Among the mutations, D126N allosterically disturbs the position of the Fe2+ ion. The mutations decrease the binding affinity toward the PZA drug
malfunction
mutations in the pncA gene cause pyrazinamide (PZA) resistance in Mycobacterium tuberculosis
malfunction
pyrazinamide (PZA)-resistance in Mycobacterium tuberculosis strains is caused by point mutations in the PZase enzyme which is the activator of the prodrug pyrazinoic acid (PZA)
malfunction
the residues of flap region of enzyme mutant K96R acquire more flexibility in mutant form of protein and thus move away from the active site. This leads to weak binding of the drug to the target residues which might interfere with the activation of the drug to functional form thereby giving rise to drug resistant bacterial strains
physiological function
pyrazinamidase (PZase) is involved in degradation of pyrazinamide to ammonia and pyrazinoic acid
physiological function
pyrazinamidase (PZase), a metalloenzyme, is responsible for acidic modification of pyrazinamide (PZA), a drug used in tuberculosis treatment
physiological function
pyrazinamidase, activator for pyrazinamide, leads to resistance against the drug pyrazinamide due to mutagenicity across the world
physiological function
pyrazinamide (PZA) is a prodrug that is converted to pyrazinoic acid (PoA, active form) by the pyrazinamidase (PZase) of Mycobacterium tuberculosis
physiological function
pyrazinamide (PZA) is an important component of first-line antituberculosis drugs activated by Mycobacterium tuberculosis pyrazinamidase (PZase) into its active form pyrazinoic acid (PZA)
physiological function
role of flap region present in PncA protein in development of resistance to the drug, molecular dynamics simulations
physiological function
the mycobacterial enzyme pyrazinamidase (PZase), is the target of pyrazinamide (PZA), one of the first-line medications for treatment of tuberculosis. PZA is a prodrug catalyzed to its active form pyrazinoic acid (POA) by enzyme PZase. POA is pumped out of the cell slowly and converts to its conjugate acid form to easily diffuse inwards and accumulates
malfunction
-
a nonfunctional PZase in resistant strains allows the mycobacterium to survive in the presence of pyrazinamide. Alternative or complementary mechanism of resistance may exist
malfunction
the major cause of PZA-resistance is associated with mutations in the pncA gene. Several novel mutations including V131F, Q141P, R154T, A170P, and V180F in the pncA gene of PZA-resistant isolates are detectetd during PZA drug susceptibility testing followed by pncA gene sequencing. Molecular mechanism of PZA-resistance, molecular dynamics
additional information
structural modeling of the enzyme homodimer, docking study and molecular dynamics simulations, overview
additional information
catalytic Cys138
additional information
-
catalytic Cys138
additional information
computational insights into pH-dependence of structure and dynamics of pyrazinamidase, comparison of wild-type and mutant enzymes, molecular dynamics simulations using the wild-type structure, PDB ID 3PL1, detailed overview. The 51-71 flap region exhibits a drastic displacement leading to enlargement of binding cavity, especially at the lower pH. Residues D8, K96, and C138 comprise an active site
additional information
development and validation of a simplified pyrazinamidase test by modifying Wayne's pyrazinamidase test for pyrazinamide drug susceptibility in Mycobacterium tuberculosis using a total of 120 complex strains/isolates, including 118 clinical isolates, and also Myycobacetrium bovis strain BCG (Tokyo substrain) and strain H37Rv, overview
additional information
-
development and validation of a simplified pyrazinamidase test by modifying Wayne's pyrazinamidase test for pyrazinamide drug susceptibility in Mycobacterium tuberculosis using a total of 120 complex strains/isolates, including 118 clinical isolates, and also Myycobacetrium bovis strain BCG (Tokyo substrain) and strain H37Rv, overview
additional information
residues Asp8, Lys96, and Cys138 form the catalytic triad. Receptor and ligand docking, molecular dynamics simulations, overview
additional information
-
residues Asp8, Lys96, and Cys138 form the catalytic triad. Receptor and ligand docking, molecular dynamics simulations, overview
additional information
stability and structure of recombinant pyrazinamidase (PZase) from Mycobacterium tuberculosis are analyzed in the presence of stabilizing osmolytes sorbitol, sucrose and glycerol, and alcohols methanol, ethanol, isopropanol and n-propanol, overview
additional information
-
stability and structure of recombinant pyrazinamidase (PZase) from Mycobacterium tuberculosis are analyzed in the presence of stabilizing osmolytes sorbitol, sucrose and glycerol, and alcohols methanol, ethanol, isopropanol and n-propanol, overview
additional information
structural and quantum mechanical computations to elucidate the altered binding mechanism of metal and drug with Mycobacterium tuberculosis pyrazinamidase due to mutagenicity. Residues Asp8, Lys96, and Cys138 play a pivotal role in catalysis
additional information
-
structural and quantum mechanical computations to elucidate the altered binding mechanism of metal and drug with Mycobacterium tuberculosis pyrazinamidase due to mutagenicity. Residues Asp8, Lys96, and Cys138 play a pivotal role in catalysis
additional information
structure analysis by molecular dynamics (MD) simulations, and spectroscopic methods, such as fluorescence spectroscopy and circular dichroism (CD)
additional information
-
structure analysis by molecular dynamics (MD) simulations, and spectroscopic methods, such as fluorescence spectroscopy and circular dichroism (CD)
additional information
structure predictions of wild-type and mutant enzymes from sequences, modeling
additional information
-
structure predictions of wild-type and mutant enzymes from sequences, modeling
additional information
the coordination of metal cofactors Ni2+, Co2+, or Fe2+ to PZase facilitates the deprotonation of coordinates water molecules to generate a nucleophile that catalyzes the enzymatic reaction
additional information
the most important catalytically important binding residues are Asp 8, Phe13, IIe133, Ala134 and Cys138 of native and mutant structures, substrate binding cavity structure analysis, and protein-ligand interaction analysis and hydrophobic interaction patterns, docking and molecular dynamics simulations of the docked complexes, overview
additional information
-
the most important catalytically important binding residues are Asp 8, Phe13, IIe133, Ala134 and Cys138 of native and mutant structures, substrate binding cavity structure analysis, and protein-ligand interaction analysis and hydrophobic interaction patterns, docking and molecular dynamics simulations of the docked complexes, overview
additional information
-
the active site residues are Asp8, Lys96, and Cys138, structure-function relationship and catalytic mechanism, overview. Homology structure modeling of wild-type and mutant enzymes, molecular substrate docking and molecular dynamics simulations, overview
additional information
wild-type and mutant PZase structures in apo and complex with pyrazinamide (PZA) are subjected to structure analysis by molecular dynamics simulations
additional information
-
wild-type and mutant PZase structures in apo and complex with pyrazinamide (PZA) are subjected to structure analysis by molecular dynamics simulations
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A146V
naturally occuring mutation, the mutant shows 72% reduced activity compared to wild-type, resistant strain
C138Y
site-directed mutagenesis
D126N
site-directed mutagenesis, the mutation causes pyrazinamide resistance, the mutation is located outside of active site and has an allosteric affect
D136G
site-directed mutagenesis, the mutation highly reduces the mutant activity compared to wild-type
D63A
naturally occuring mutation, susceptible strain
E144K
naturally occuring mutation from PZA-resistant isolate, analysis of the resistance mechanism of the mutant strain
F94L
site-directed mutagenesis
G24D
site-directed mutagenesis
G97D
naturally occuring mutation, the mutant shows 90% reduced activity compared to wild-type, resistant strain
H51P
naturally occuring mutation, inactive mutant, resistant strain
H51Q
site-directed mutagenesis
I5T
naturally occuring mutation, the mutant shows 88% reduced activity compared to wild-type, resistant strain
I6L
naturally occuring mutation, susceptible strain
K96R
naturally occurring mutation in the PncA catalytic region, binding cavity analysis shows an increase of 762.3 A3 in the volume of the mutant protein. Docking studies reveal that pyrazinamide (PZA) has a greater binding affinity for the wild-type protein in comparison to the mutant protein. The residues of flap region acquire more flexibility in mutant form of protein and thus move away from the active site. This leads to weak binding of the drug to the target residues. The mutation leads to a substantial increase in the binding cavity. This prohibits the enzyme from holding the drug properly and therefore pyrazinoic acid (PZA) cannot take its active form
L116P
site-directed mutagenesis
L19R
naturally occuring mutation from PZA-resistant isolate
L85P
naturally occuring mutation, resistant strain
L85R
naturally occuring mutation, inactive mutant, resistant strain
M175V
naturally occuring mutation, susceptible strain
N11K
site-directed mutagenesis, the active site mutation causes pyrazinamide resistance, destabilization of the Fe2+ binding site
P62T
naturally occuring mutation, susceptible strain
P69T
site-directed mutagenesis, the active site mutation causes pyrazinamide resistance, destabilization of the Fe2+ binding site
P77L/V131G
naturally occuring mutation, susceptible strain
R140H
naturally occuring mutation from PZA-resistant isolate
R140S
naturally occuring mutation, susceptible strain
S67P
site-directed mutagenesis
T167I
naturally occuring mutation, susceptible strain
T47A
naturally occuring mutation, susceptible strain
T47P
naturally occuring mutation, inactive mutant, resistant strain
T87M
site-directed mutagenesis, active mutant, susceptible strain
T92C
the naturally occuring mutation causes an increase in distance from metal ion position to enzyme active site, but it is considered as a polymorphism
V155G
naturally occuring mutation, resistant strain
V7A
naturally occuring mutation, susceptible strain
V9A
naturally occuring mutation, the mutant shows 73% reduced activity compared to wild-type, resistant strain
V9G
naturally occuring mutation, the mutant shows 99% reduced activity compared to wild-type, resistant strain
W68G
naturally occuring mutation, resistant strain
Y64D
naturally occuring mutation, susceptible strain
Y99S
naturally occuring mutation, susceptible strain
A143T
-
site-directed mutagenesis, the mutation decreases the Km and kcat values of the enzyme
A143T/T168A/E173K
-
site-directed mutagenesis, the mutation decreases the Km and kcat values of the enzyme, the mutant shows reduced thermostability compared to wild-type
L151S
-
site-directed mutagenesis, the mutant has a weakened binding affinity for pyrazinamide and reduced thermostability compared to the wild-type
D12A
site-directed mutagenesis
D12A
site-directed mutagenesis, the mutation highly reduces the mutant activity compared to wild-type
D12G
site-directed mutagenesis
D12G
site-directed mutagenesis, the mutation highly reduces the mutant activity compared to wild-type
D49N
site-directed mutagenesis
D49N
site-directed mutagenesis, the mutation highly reduces the mutant activity compared to wild-type and has a deleterious effect on the metal binding mechanism of PZase
G78C
site-directed mutagenesis
G78C
site-directed mutagenesis, the mutation highly reduces the mutant activity compared to wild-type and has a deleterious effect on the metal binding mechanism of PZase
H51R
naturally occuring mutation, inactive mutant, resistant strain
H51R
site-directed mutagenesis, the mutation highly reduces the mutant activity compared to wild-type and has a deleterious effect on the metal binding mechanism of PZase
H57D
site-directed mutagenesis
H57D
naturally occuring mutation, inactive mutant, resistant strain
T135P
site-directed mutagenesis
T135P
site-directed mutagenesis, the mutation highly reduces the mutant activity compared to wild-type
T142R
naturally occuring mutation, inactive mutant, resistant strain
T142R
naturally occuring mutation, resistant strain
additional information
analysis of the specific pyrazinamidase (PZase) activity of PncA mutants via PCR-based in vitro-synthesized-PZase assay and correlation of the results to the pyrazinamide (PZA) susceptibility phenotype determined by culture in acidic agar medium at pH 6.0. A set of 23 clinical isolates displaying mutated pncA genes (11 PZA-resistant and 12 PZA-susceptible) and 55 PZA-susceptible clinical strains displaying a wild-type pncA gene are tested. Among the 23 mutants tested, 4 corresponded to mutations not reported before (I5T, Y99S, T142R, and P77L/V131G). Of the 11 PncA mutants expressed from PZA-resistant clinical isolates, 9 are expressed in vitro at yields above 50% relative to the wild-type enzyme. Among them, 6 enzymes (T47P, H51P, H51R, H57D, L85R and T142R) show no detectable activity, while the relative activities for the 3 others, V9A, G97D, and A146V, are low compared to the wild-type PZase. The remaining two mutants, I5T and V9G, presented very low relative expression (5%) and relative activities values of 12 and 1%, respectively. Twelve mutants are expressed from PZA-susceptible isolates. Their expression arte is similar to the wild-type enzyme, and they behave as active pyrazinamidase with specific relative activities ranging from 34 to 314%. Finally, discrepant results are observed for two mutants, V7A and P62T
additional information
-
analysis of the specific pyrazinamidase (PZase) activity of PncA mutants via PCR-based in vitro-synthesized-PZase assay and correlation of the results to the pyrazinamide (PZA) susceptibility phenotype determined by culture in acidic agar medium at pH 6.0. A set of 23 clinical isolates displaying mutated pncA genes (11 PZA-resistant and 12 PZA-susceptible) and 55 PZA-susceptible clinical strains displaying a wild-type pncA gene are tested. Among the 23 mutants tested, 4 corresponded to mutations not reported before (I5T, Y99S, T142R, and P77L/V131G). Of the 11 PncA mutants expressed from PZA-resistant clinical isolates, 9 are expressed in vitro at yields above 50% relative to the wild-type enzyme. Among them, 6 enzymes (T47P, H51P, H51R, H57D, L85R and T142R) show no detectable activity, while the relative activities for the 3 others, V9A, G97D, and A146V, are low compared to the wild-type PZase. The remaining two mutants, I5T and V9G, presented very low relative expression (5%) and relative activities values of 12 and 1%, respectively. Twelve mutants are expressed from PZA-susceptible isolates. Their expression arte is similar to the wild-type enzyme, and they behave as active pyrazinamidase with specific relative activities ranging from 34 to 314%. Finally, discrepant results are observed for two mutants, V7A and P62T
additional information
cumulative effect of mutations and iron substitution
additional information
-
cumulative effect of mutations and iron substitution
additional information
molecular dynamics simulations coupled with essential dynamics and binding pocket analysis at neutral (pH = 7) and acidic (pH = 4) ambient conditions, detailed overview. Computational insights into pH-dependence of structure and dynamics of pyrazinamidase, comparison of wild-type and mutant enzymes
additional information
-
molecular modeling and substrate docking reveals that the wild-type has much stronger binding affinity to PZA than the mutants whereas mutant L151S has the weakest binding affinity. Molecular dynamics simulations and the essential dynamics results illustrate that the positions of the 51st to 71st residues are more dynamics in mutant L151S as compared to the other atoms in PZase. Kinetics of activation and half-life of wild-type and mutant PZases
additional information
-
mutational statistics, especially mutations in the promoter region of pncA, Analysis of methods of phenotypic determination and genotype-phenotype evaluation for diagnostics in clinical drug studies and MIC determinations, overview. For diagnostics, individual mutations (or any subset) are not sufficiently sensitive. Assuming similar error profiles of the 5 phenotyping platforms included in the study, the entire enzyme and its promoter provide a combined estimated sensitivity of 83%. Molecular diagnostics of PZA resistance
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Rueda, D.; Sheen, P.; Gilman, R.H.; Bueno, C.; Santos, M.; Pando-Robles, V.; Batista, C.V.; Zimic, M.
Nicotinamidase/pyrazinamidase of Mycobacterium tuberculosis forms homo-dimers stabilized by disulfide bonds
Tuberculosis
94
644-648
2014
Mycobacterium tuberculosis (I6XD65), Mycobacterium tuberculosis H37Rv (I6XD65)
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Systematic review of mutations in pyrazinamidase associated with pyrazinamide resistance in Mycobacterium tuberculosis clinical isolates
Antimicrob. Agents Chemother.
59
5267-5277
2015
Mycobacterium tuberculosis
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Vats, C.; Dhanjal, J.; Goyal, S.; Gupta, A.; Bharadvaja, N.; Grover, A.
Mechanistic analysis elucidating the relationship between Lys96 mutation in Mycobacterium tuberculosis pyrazinamidase enzyme and pyrazinamide susceptibility
BMC Genomics
16(Suppl 2)
S14
2015
Mycobacterium tuberculosis (I6XD65), Mycobacterium tuberculosis, Mycobacterium tuberculosis ATCC 25618 (I6XD65), Mycobacterium tuberculosis H37Rv (I6XD65)
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Revelation of enzyme activity of mutant pyrazinamidases from Mycobacterium tuberculosis upon binding with various metals using quantum mechanical approach
Comput. Biol. Chem.
83
107108
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Mycobacterium tuberculosis (I6XD65), Mycobacterium tuberculosis, Mycobacterium tuberculosis ATCC 25618 (I6XD65), Mycobacterium tuberculosis H37Rv (I6XD65)
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The combinatorial effects of osmolytes and alcohols on the stability of pyrazinamidase methanol affects the enzyme stability through hydrophobic interactions and hydrogen bonds
Int. J. Biol. Macromol.
108
1339-1347
2018
Mycobacterium tuberculosis (I6XD65), Mycobacterium tuberculosis, Mycobacterium tuberculosis ATCC 25618 (I6XD65), Mycobacterium tuberculosis H37Rv (I6XD65)
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Effects of sorbitol and glycerol on the structure, dynamics, and stability of Mycobacterium tuberculosis pyrazinamidase
Int. J. Mycobacteriol.
5 Suppl 1
S138-S139
2016
Mycobacterium tuberculosis (I6XD65), Mycobacterium tuberculosis, Mycobacterium tuberculosis ATCC 25618 (I6XD65), Mycobacterium tuberculosis H37Rv (I6XD65)
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Rueda, D.; Bernard, C.; Gandy, L.; Capton, E.; Boudjelloul, R.; Brossier, F.; Veziris, N.; Zimic, M.; Sougakoff, W.
Estimation of pyrazinamidase activity using a cell-free in vitro synthesis of pnca and its association with pyrazinamide susceptibility in Mycobacterium tuberculosis
Int. J. Mycobacteriol.
7
16-25
2018
Mycobacterium tuberculosis (I6XD65), Mycobacterium tuberculosis, Mycobacterium tuberculosis ATCC 25618 (I6XD65), Mycobacterium tuberculosis H37Rv (I6XD65), Mycobacterium tuberculosis variant bovis
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Structural dynamics behind variants in pyrazinamidase and pyrazinamide resistance
J. Biomol. Struct. Dyn.
38
3003-3017
2020
Mycobacterium tuberculosis (A0A2Z5CVM9), Mycobacterium tuberculosis
brenda
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Computational insights into pH-dependence of structure and dynamics of pyrazinamidase A comparison of wild type and mutants
J. Cell. Biochem.
120
2502-2514
2018
Mycobacterium tuberculosis (I6XD65), Mycobacterium tuberculosis ATCC 25618 (I6XD65), Mycobacterium tuberculosis H37Rv (I6XD65)
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Pyrazinamide resistance and mutations L19R, R140H, and E144K in pyrazinamidase of Mycobacterium tuberculosis
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120
7154-7166
2019
Mycobacterium tuberculosis (I6XD65), Mycobacterium tuberculosis, Mycobacterium tuberculosis ATCC 25618 (I6XD65), Mycobacterium tuberculosis H37Rv (I6XD65)
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Insights into the mechanisms of the pyrazinamide resistance of three pyrazinamidase mutants N11K, P69T, and D126N
J. Chem. Inf. Model.
59
498-508
2019
Mycobacterium tuberculosis (I6XD65), Mycobacterium tuberculosis, Mycobacterium tuberculosis ATCC 25618 (I6XD65), Mycobacterium tuberculosis H37Rv (I6XD65)
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Aono, A.; Chikamatsu, K.; Yamada, H.; Igarashi, Y.; Murase, Y.; Takaki, A.; Mitarai, S.
A simplified pyrazinamidase test for pyrazinamide drug susceptibility in Mycobacterium tuberculosis
J. Microbiol. Methods
154
52-54
2018
Mycobacterium tuberculosis (I6XD65), Mycobacterium tuberculosis, Mycobacterium tuberculosis ATCC 25618 (I6XD65), Mycobacterium tuberculosis H37Rv (I6XD65)
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Effects of metal-ion replacement on pyrazinamidase activity a quantum mechanical study
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73
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2017
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Structural and quantum mechanical computations to elucidate the altered binding mechanism of metal and drug with pyrazinamidase from Mycobacterium tuberculosis due to mutagenicity
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80
126-131
2018
Mycobacterium tuberculosis (I6XD65), Mycobacterium tuberculosis, Mycobacterium tuberculosis ATCC 25618 (I6XD65), Mycobacterium tuberculosis H37Rv (I6XD65)
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2015
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Insights into pyrazinamidase and DNA gyrase protein structures in resistant and susceptible clinical isolates of Mycobacterium tuberculosis
Tanaffos
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147-153
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Mycobacterium tuberculosis (I6XD65), Mycobacterium tuberculosis, Mycobacterium tuberculosis ATCC 25618 (I6XD65), Mycobacterium tuberculosis H37Rv (I6XD65)
brenda