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Metal-ion effects on the polarization of metal-bound water and infrared vibrational modes of the coordinated metal center of Mycobacterium tuberculosis pyrazinamidase via quantum mechanical calculations.

Salazar-Salinas K, Baldera-Aguayo PA, Encomendero-Risco JJ, Orihuela M, Sheen P, Seminario JM, Zimic M - J Phys Chem B (2014)

Bottom Line: We use quantum mechanical calculations to investigate the Zn(2+), Fe(2+), and Mn(2+) metal cofactor effects on the local MCS structure, metal-ligand or metal-residue binding energy, and charge distribution.This suggests that the coordination of Zn(2+) or Mn(2+) to the PZAse protein facilitates the deprotonation of coordinated water to generate a nucleophile for catalysis as in carboxypeptidase A.Because metal ion binding is relevant to enzymatic reaction, identification of the metal binding event is important.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio de Bioinformática y Biología Molecular, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia , San Martin de Porres, Lima 31 Lima, Perú

ABSTRACT
Mycobacterium tuberculosis pyrazinamidase (PZAse) is a key enzyme to activate the pro-drug pyrazinamide (PZA). PZAse is a metalloenzyme that coordinates in vitro different divalent metal cofactors in the metal coordination site (MCS). Several metals including Co(2+), Mn(2+), and Zn(2+) are able to reactivate the metal-depleted PZAse in vitro. We use quantum mechanical calculations to investigate the Zn(2+), Fe(2+), and Mn(2+) metal cofactor effects on the local MCS structure, metal-ligand or metal-residue binding energy, and charge distribution. Results suggest that the major metal-dependent changes occur in the metal-ligand binding energy and charge distribution. Zn(2+) shows the highest binding energy to the ligands (residues). In addition, Zn(2+) and Mn(2+) within the PZAse MCS highly polarize the O-H bond of coordinated water molecules in comparison with Fe(2+). This suggests that the coordination of Zn(2+) or Mn(2+) to the PZAse protein facilitates the deprotonation of coordinated water to generate a nucleophile for catalysis as in carboxypeptidase A. Because metal ion binding is relevant to enzymatic reaction, identification of the metal binding event is important. The infrared vibrational mode shift of the C═Nε (His) bond from the M. tuberculosis MCS is the best IR probe to metal complexation.

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Comparison of far-infrared intensity spectra for (a) Zn-,(b) Fe-,and (c) Mn-coordinated complexes in aqueous and gas phases in the500–0 cm–1 region. Calculated bond stretchingmodes from metal-coordinated complexes are indicated by arrows, aswell as experimental bond stretching from analogue structures. Thestretching mode of metal–O(H2O) is represented byν1, metal–O(Asp) by ν2 and metal–Nε(His) by ν3. Experimental values are denoted by single primemark.
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fig4: Comparison of far-infrared intensity spectra for (a) Zn-,(b) Fe-,and (c) Mn-coordinated complexes in aqueous and gas phases in the500–0 cm–1 region. Calculated bond stretchingmodes from metal-coordinated complexes are indicated by arrows, aswell as experimental bond stretching from analogue structures. Thestretching mode of metal–O(H2O) is represented byν1, metal–O(Asp) by ν2 and metal–Nε(His) by ν3. Experimental values are denoted by single primemark.

Mentions: Among coordination bonds, the Me-Nε bond typeis much tighterthan Me-O (Table 7). The bond force constantfor Me–Nε bond type decreases as Fe–Nε >Zn–Nε > Mn–Nε, and for the Me–O(Asp/H2O) bond type as Fe–O > Zn–O > Mn–O.TheO66–H67 and O77–H78 bonds are significantly more flexiblethan the other O–H bond from the corresponding coordinatedwater molecule, because the hydrogen atom of these bonds (H67 andH78) forms a hydrogen bond with Asp49. Results suggest that H67 andH68 are more feasible to be donated. Figure 4 compares the calculated IR spectra of metal complexes in the gasand aqueous phases.


Metal-ion effects on the polarization of metal-bound water and infrared vibrational modes of the coordinated metal center of Mycobacterium tuberculosis pyrazinamidase via quantum mechanical calculations.

Salazar-Salinas K, Baldera-Aguayo PA, Encomendero-Risco JJ, Orihuela M, Sheen P, Seminario JM, Zimic M - J Phys Chem B (2014)

Comparison of far-infrared intensity spectra for (a) Zn-,(b) Fe-,and (c) Mn-coordinated complexes in aqueous and gas phases in the500–0 cm–1 region. Calculated bond stretchingmodes from metal-coordinated complexes are indicated by arrows, aswell as experimental bond stretching from analogue structures. Thestretching mode of metal–O(H2O) is represented byν1, metal–O(Asp) by ν2 and metal–Nε(His) by ν3. Experimental values are denoted by single primemark.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4514207&req=5

fig4: Comparison of far-infrared intensity spectra for (a) Zn-,(b) Fe-,and (c) Mn-coordinated complexes in aqueous and gas phases in the500–0 cm–1 region. Calculated bond stretchingmodes from metal-coordinated complexes are indicated by arrows, aswell as experimental bond stretching from analogue structures. Thestretching mode of metal–O(H2O) is represented byν1, metal–O(Asp) by ν2 and metal–Nε(His) by ν3. Experimental values are denoted by single primemark.
Mentions: Among coordination bonds, the Me-Nε bond typeis much tighterthan Me-O (Table 7). The bond force constantfor Me–Nε bond type decreases as Fe–Nε >Zn–Nε > Mn–Nε, and for the Me–O(Asp/H2O) bond type as Fe–O > Zn–O > Mn–O.TheO66–H67 and O77–H78 bonds are significantly more flexiblethan the other O–H bond from the corresponding coordinatedwater molecule, because the hydrogen atom of these bonds (H67 andH78) forms a hydrogen bond with Asp49. Results suggest that H67 andH68 are more feasible to be donated. Figure 4 compares the calculated IR spectra of metal complexes in the gasand aqueous phases.

Bottom Line: We use quantum mechanical calculations to investigate the Zn(2+), Fe(2+), and Mn(2+) metal cofactor effects on the local MCS structure, metal-ligand or metal-residue binding energy, and charge distribution.This suggests that the coordination of Zn(2+) or Mn(2+) to the PZAse protein facilitates the deprotonation of coordinated water to generate a nucleophile for catalysis as in carboxypeptidase A.Because metal ion binding is relevant to enzymatic reaction, identification of the metal binding event is important.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio de Bioinformática y Biología Molecular, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia , San Martin de Porres, Lima 31 Lima, Perú

ABSTRACT
Mycobacterium tuberculosis pyrazinamidase (PZAse) is a key enzyme to activate the pro-drug pyrazinamide (PZA). PZAse is a metalloenzyme that coordinates in vitro different divalent metal cofactors in the metal coordination site (MCS). Several metals including Co(2+), Mn(2+), and Zn(2+) are able to reactivate the metal-depleted PZAse in vitro. We use quantum mechanical calculations to investigate the Zn(2+), Fe(2+), and Mn(2+) metal cofactor effects on the local MCS structure, metal-ligand or metal-residue binding energy, and charge distribution. Results suggest that the major metal-dependent changes occur in the metal-ligand binding energy and charge distribution. Zn(2+) shows the highest binding energy to the ligands (residues). In addition, Zn(2+) and Mn(2+) within the PZAse MCS highly polarize the O-H bond of coordinated water molecules in comparison with Fe(2+). This suggests that the coordination of Zn(2+) or Mn(2+) to the PZAse protein facilitates the deprotonation of coordinated water to generate a nucleophile for catalysis as in carboxypeptidase A. Because metal ion binding is relevant to enzymatic reaction, identification of the metal binding event is important. The infrared vibrational mode shift of the C═Nε (His) bond from the M. tuberculosis MCS is the best IR probe to metal complexation.

Show MeSH
Related in: MedlinePlus