EC Number | Protein Variants | Comment | Organism |
---|---|---|---|
3.5.1.B15 | 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 | Mycobacterium tuberculosis |
EC Number | Metals/Ions | Comment | Organism | Structure |
---|---|---|---|---|
3.5.1.B15 | Fe2+ | the enzyme contains a Fe2+ ion surrounded by one aspartate and three histidines in the substrate binding cavity along with three water molecules | Mycobacterium tuberculosis |
EC Number | Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|---|
3.5.1.B15 | pyrazinamide + H2O | Mycobacterium tuberculosis | - |
pyrazinoic acid + NH3 | - |
? | |
3.5.1.B15 | pyrazinamide + H2O | Mycobacterium tuberculosis H37Rv | - |
pyrazinoic acid + NH3 | - |
? | |
3.5.1.B15 | pyrazinamide + H2O | Mycobacterium tuberculosis ATCC 25618 | - |
pyrazinoic acid + NH3 | - |
? |
EC Number | Organism | UniProt | Comment | Textmining |
---|---|---|---|---|
3.5.1.B15 | Mycobacterium tuberculosis | I6XD65 | - |
- |
3.5.1.B15 | Mycobacterium tuberculosis ATCC 25618 | I6XD65 | - |
- |
3.5.1.B15 | Mycobacterium tuberculosis H37Rv | I6XD65 | - |
- |
EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|---|
3.5.1.B15 | pyrazinamide + H2O | - |
Mycobacterium tuberculosis | pyrazinoic acid + NH3 | - |
? | |
3.5.1.B15 | pyrazinamide + H2O | enzyme protein ligand interaction, docking study using the wild-type PncA protein structure (PDB ID 3PL1), overview | Mycobacterium tuberculosis | pyrazinoic acid + NH3 | - |
? | |
3.5.1.B15 | pyrazinamide + H2O | - |
Mycobacterium tuberculosis H37Rv | pyrazinoic acid + NH3 | - |
? | |
3.5.1.B15 | pyrazinamide + H2O | enzyme protein ligand interaction, docking study using the wild-type PncA protein structure (PDB ID 3PL1), overview | Mycobacterium tuberculosis H37Rv | pyrazinoic acid + NH3 | - |
? | |
3.5.1.B15 | pyrazinamide + H2O | - |
Mycobacterium tuberculosis ATCC 25618 | pyrazinoic acid + NH3 | - |
? | |
3.5.1.B15 | pyrazinamide + H2O | enzyme protein ligand interaction, docking study using the wild-type PncA protein structure (PDB ID 3PL1), overview | Mycobacterium tuberculosis ATCC 25618 | pyrazinoic acid + NH3 | - |
? |
EC Number | Synonyms | Comment | Organism |
---|---|---|---|
3.5.1.B15 | PncA | - |
Mycobacterium tuberculosis |
EC Number | General Information | Comment | Organism |
---|---|---|---|
3.5.1.B15 | 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 | Mycobacterium tuberculosis |
3.5.1.B15 | 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 | Mycobacterium tuberculosis |
3.5.1.B15 | 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 | Mycobacterium tuberculosis |
3.5.1.B15 | physiological function | role of flap region present in PncA protein in development of resistance to the drug, molecular dynamics simulations | Mycobacterium tuberculosis |