3.5.1.B15: pyrazinamidase

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

cumulative effect of mutations and iron substitution

756516

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

757008

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

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

757305

Mycobacteroides abscessus

mutations in the pncA gene cause pyrazinamide (PZA) resistance in Mycobacterium tuberculosis

758499

B1MLY1

Mycobacterium abscessus is resistant to pyrazinamide due to the random mutations in the primary sequences of the pyrazinamidase. In silico structural characterizations of pyrazinamidase variants from various species of Mycobacterium

Mycobacterium avium

P94914

Mycobacterium avium is resistant to pyrazinamide due to the random mutations in the primary sequences of the pyrazinamidase. In silico structural characterizations of pyrazinamidase variants from various species of Mycobacterium

Mycobacterium tuberculosis variant bovis

U5TP36

Mycobacterium bovis is resistant to pyrazinamide due to the random mutations in the primary sequences of the pyrazinamidase. In silico structural characterizations of pyrazinamidase variants from various species of Mycobacterium

Mycobacterium kansasii

O07691

Mycobacterium kansasii is resistant to pyrazinamide due to the random mutations in the primary sequences of the pyrazinamidase. In silico structural characterizations of pyrazinamidase variants from various species of Mycobacterium

Mycobacterium marinum

A0A3E2MTZ2

Mycobacterium marinum is resistant to pyrazinamide due to the random mutations in the primary sequences of the pyrazinamidase. In silico structural characterizations of pyrazinamidase variants from various species of Mycobacterium

Mycolicibacterium smegmatis

Q9ZF59

Mycobacterium smegmatis is resistant to pyrazinamide due to the random mutations in the primary sequences of the pyrazinamidase. In silico structural characterizations of pyrazinamidase variants from various species of Mycobacterium

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)

A0A2Z5CVM9

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

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

Mycobacteroides abscessus JCM 13569

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Mycobacterium abscessus is resistant to pyrazinamide due to the random mutations in the primary sequences of the pyrazinamidase. In silico structural characterizations of pyrazinamidase variants from various species of Mycobacterium

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Mycobacteroides abscessus CIP 104536

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Mycobacterium abscessus is resistant to pyrazinamide due to the random mutations in the primary sequences of the pyrazinamidase. In silico structural characterizations of pyrazinamidase variants from various species of Mycobacterium

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Mycobacteroides abscessus DSM 44196

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Mycobacterium abscessus is resistant to pyrazinamide due to the random mutations in the primary sequences of the pyrazinamidase. In silico structural characterizations of pyrazinamidase variants from various species of Mycobacterium

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Mycobacteroides abscessus ATCC 19977

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Mycobacterium abscessus is resistant to pyrazinamide due to the random mutations in the primary sequences of the pyrazinamidase. In silico structural characterizations of pyrazinamidase variants from various species of Mycobacterium

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Mycobacteroides abscessus NCTC 13031

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Mycobacterium abscessus is resistant to pyrazinamide due to the random mutations in the primary sequences of the pyrazinamidase. In silico structural characterizations of pyrazinamidase variants from various species of Mycobacterium

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Mycobacteroides abscessus TMC 1543

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Mycobacterium abscessus is resistant to pyrazinamide due to the random mutations in the primary sequences of the pyrazinamidase. In silico structural characterizations of pyrazinamidase variants from various species of Mycobacterium

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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

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cumulative effect of mutations and iron substitution

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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)

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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

-

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

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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

-

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

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mutations in the pncA gene cause pyrazinamide (PZA) resistance in Mycobacterium tuberculosis

-

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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

-

cumulative effect of mutations and iron substitution

-

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)

-

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

-

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

-

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

-

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

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mutations in the pncA gene cause pyrazinamide (PZA) resistance in Mycobacterium tuberculosis

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metabolism

Acinetobacter baumannii

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in Mycobacterium tuberculosis the enzyme converts the nicotinamide analogue prodrug pyrazinamide into the bacteriostatic pyrazinoic acid

710862

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

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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

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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

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physiological function

Acinetobacter baumannii

-

the reaction product pyrazinoic acid inhibits Mycobacterium tuberculosis type I fatty acid synthase, represses mycolic acid biosynthesis, and appears to affect membrane energetics and acidification of the cytoplasm

710862

Bacillus subtilis

-

nicotinamidase/pyrazinamidase PncA catalyzes the deamination of nicotinamide to nicotinic acid (EC 3.5.1.19). PncA also functions as a pyrazinamidase in a wide variety of eubacteria and is an essential coenzyme in many cellular redox reactions in living systems

752683

pyrazinamidase (PZase) is involved in degradation of pyrazinamide to ammonia and pyrazinoic acid

pyrazinamidase (PZase), a metalloenzyme, is responsible for acidic modification of pyrazinamide (PZA), a drug used in tuberculosis treatment

757445

pyrazinamidase, activator for pyrazinamide, leads to resistance against the drug pyrazinamide due to mutagenicity across the world

pyrazinamide (PZA) is a prodrug that is converted to pyrazinoic acid (PoA, active form) by the pyrazinamidase (PZase) of Mycobacterium tuberculosis

757425

A0A2Z5CVM9

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)

pyrazinamide (PZA) is an important component of first-line antituberculosis drugs activated by Mycobacterium tuberculosis pyrazinamidase (PZase) into its active form pyrazinoic acid (PZA)

role of flap region present in PncA protein in development of resistance to the drug, molecular dynamics simulations

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

757291

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role of flap region present in PncA protein in development of resistance to the drug, molecular dynamics simulations

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pyrazinamidase (PZase) is involved in degradation of pyrazinamide to ammonia and pyrazinoic acid

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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

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pyrazinamide (PZA) is an important component of first-line antituberculosis drugs activated by Mycobacterium tuberculosis pyrazinamidase (PZase) into its active form pyrazinoic acid (PZA)

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pyrazinamide (PZA) is a prodrug that is converted to pyrazinoic acid (PoA, active form) by the pyrazinamidase (PZase) of Mycobacterium tuberculosis

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pyrazinamidase (PZase), a metalloenzyme, is responsible for acidic modification of pyrazinamide (PZA), a drug used in tuberculosis treatment

-

pyrazinamidase, activator for pyrazinamide, leads to resistance against the drug pyrazinamide due to mutagenicity across the world

-

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role of flap region present in PncA protein in development of resistance to the drug, molecular dynamics simulations

-

pyrazinamidase (PZase) is involved in degradation of pyrazinamide to ammonia and pyrazinoic acid

-

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

-

pyrazinamide (PZA) is an important component of first-line antituberculosis drugs activated by Mycobacterium tuberculosis pyrazinamidase (PZase) into its active form pyrazinoic acid (PZA)

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pyrazinamide (PZA) is a prodrug that is converted to pyrazinoic acid (PoA, active form) by the pyrazinamidase (PZase) of Mycobacterium tuberculosis

-

pyrazinamidase (PZase), a metalloenzyme, is responsible for acidic modification of pyrazinamide (PZA), a drug used in tuberculosis treatment

-

pyrazinamidase, activator for pyrazinamide, leads to resistance against the drug pyrazinamide due to mutagenicity across the world

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additional information

Acinetobacter baumannii

B0VA03

protein conformational changes after ligand dissociation, molecular dynamics simulation methods are performed to investigate the unbinding process of nicotinamide using the enzyme's crystal structure. PDB ID 2WT9

735054

structural modeling of the enzyme homodimer, docking study and molecular dynamics simulations, overview

735324

catalytic Cys138

757008

-

catalytic Cys138

757008

uncultured bacterium

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combined whole-cell high-throughput functional screening for identification of nicotinamidases/pyrazinamidases in metagenomic/polygenomic libraries, screening of mesophilic marine bacteria (MB) polygenomic library. Development of two whole-cell methods using the chemical property of one of the products formed in the enzymatic reaction (pyrazinoic or NA) to form colored complexes with stable iron salts, such as ammonium ferrous sulfate or sodium nitroprusside (SNP), optimization of the assay. A fosmid polygenomic expression library obtained from deep-sea mesophilic bacteria is screened, discovering several positive clones with the ammonium ferrous sulfate method. Quantitative rescreening with the SNP method allowing the finding of the first nicotinamidase with balanced catalytic efficiency toward nicotinamidase activity (EC 3.5.1.19) and pyrazinamide (pyrazinamidase activity)

753679

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

757291

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

757425

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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

757425

residues Asp8, Lys96, and Cys138 form the catalytic triad. Receptor and ligand docking, molecular dynamics simulations, overview

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residues Asp8, Lys96, and Cys138 form the catalytic triad. Receptor and ligand docking, molecular dynamics simulations, overview

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

756937

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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

756937

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

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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

structure analysis by molecular dynamics (MD) simulations, and spectroscopic methods, such as fluorescence spectroscopy and circular dichroism (CD)

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structure analysis by molecular dynamics (MD) simulations, and spectroscopic methods, such as fluorescence spectroscopy and circular dichroism (CD)

structure predictions of wild-type and mutant enzymes from sequences, modeling

758499

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structure predictions of wild-type and mutant enzymes from sequences, modeling

758499

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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

758283

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

757445

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

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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

Mycobacterium tuberculosis variant bovis

U5TP36

the substrate binding site involves residues D8, F13, D49, K96, I133, A135, H137, and C138, binding sites architectures and GATE analysis, molecular dynamics simulations, overview

Mycobacterium kansasii

O07691

the substrate binding site involves residues D8, F13, D49, K96, I133, A135, H137, and C138, binding sites architectures and GATE analysis, molecular dynamics simulations, overview

Mycobacterium avium

P94914

the substrate binding site involves residues D8, F13, D49, K96, I133, A135, H137, and C138, binding sites architectures and GATE analysis, molecular dynamics simulations, overview

Mycolicibacterium smegmatis

Q9ZF59

the substrate binding site involves residues D8, F13, D49, K96, I133, A135, H137, and C138, binding sites architectures and GATE analysis, molecular dynamics simulations, overview

Mycobacteroides abscessus

B1MLY1

the substrate binding site involves residues D8, F13, D49, K96, I133, A135, H137, and C138, binding sites architectures and GATE analysis, molecular dynamics simulations, overview

Mycobacterium marinum

A0A3E2MTZ2

the substrate binding site involves residues D8, F13, D49, K96, I133, A135, H137, and C138, binding sites architectures and GATE analysis, molecular dynamics simulations, overview

A0A2Z5CVM9

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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wild-type and mutant PZase structures in apo and complex with pyrazinamide (PZA) are subjected to structure analysis by molecular dynamics simulations

Mycobacteroides abscessus JCM 13569

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the substrate binding site involves residues D8, F13, D49, K96, I133, A135, H137, and C138, binding sites architectures and GATE analysis, molecular dynamics simulations, overview

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Mycobacteroides abscessus CIP 104536

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the substrate binding site involves residues D8, F13, D49, K96, I133, A135, H137, and C138, binding sites architectures and GATE analysis, molecular dynamics simulations, overview

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Mycobacteroides abscessus DSM 44196

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the substrate binding site involves residues D8, F13, D49, K96, I133, A135, H137, and C138, binding sites architectures and GATE analysis, molecular dynamics simulations, overview

-

Mycobacteroides abscessus ATCC 19977

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the substrate binding site involves residues D8, F13, D49, K96, I133, A135, H137, and C138, binding sites architectures and GATE analysis, molecular dynamics simulations, overview

-

Mycobacteroides abscessus NCTC 13031

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the substrate binding site involves residues D8, F13, D49, K96, I133, A135, H137, and C138, binding sites architectures and GATE analysis, molecular dynamics simulations, overview

-

Mycobacteroides abscessus TMC 1543

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the substrate binding site involves residues D8, F13, D49, K96, I133, A135, H137, and C138, binding sites architectures and GATE analysis, molecular dynamics simulations, overview

-

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structural modeling of the enzyme homodimer, docking study and molecular dynamics simulations, overview

-

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

-

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

-

structure analysis by molecular dynamics (MD) simulations, and spectroscopic methods, such as fluorescence spectroscopy and circular dichroism (CD)

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catalytic Cys138

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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

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residues Asp8, Lys96, and Cys138 form the catalytic triad. Receptor and ligand docking, molecular dynamics simulations, overview

-

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

-

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

-

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

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structure predictions of wild-type and mutant enzymes from sequences, modeling

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