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

Karim Salazar-Salinas, Pedro A. Baldera-Aguayo, Jimy J. Encomendero-Risco, Melvin Orihuela, Patricia Sheen, Jorge M. Seminario, Mirko Zimic

Research output: Contribution to journalArticle

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 Co2+, Mn 2+, and Zn2+ are able to reactivate the metal-depleted PZAse in vitro. We use quantum mechanical calculations to investigate the Zn2+, Fe2+, and Mn2+ 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, Zn2+ and Mn2+ 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 Zn2+ 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.

Original languageEnglish (US)
Pages (from-to)10065-10075
Number of pages11
JournalJournal of Physical Chemistry B
Volume118
Issue number34
DOIs
StatePublished - 2014
Externally publishedYes

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tuberculosis
Mycobacterium tuberculosis
Metal ions
vibration mode
metal ions
Metals
Ions
Polarization
Infrared radiation
Water
polarization
metals
water
Binding energy
binding energy
Charge distribution
Ligands
pyrazinamide deamidase
charge distribution
ligands

ASJC Scopus subject areas

  • Surfaces, Coatings and Films
  • Physical and Theoretical Chemistry
  • Materials Chemistry

Cite this

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, Karim; Baldera-Aguayo, Pedro A.; Encomendero-Risco, Jimy J.; Orihuela, Melvin; Sheen, Patricia; Seminario, Jorge M.; Zimic, Mirko.

In: Journal of Physical Chemistry B, Vol. 118, No. 34, 2014, p. 10065-10075.

Research output: Contribution to journalArticle

Salazar-Salinas, Karim ; Baldera-Aguayo, Pedro A. ; Encomendero-Risco, Jimy J. ; Orihuela, Melvin ; Sheen, Patricia ; Seminario, Jorge M. ; Zimic, Mirko. / 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. In: Journal of Physical Chemistry B. 2014 ; Vol. 118, No. 34. pp. 10065-10075.
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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 Co2+, Mn 2+, and Zn2+ are able to reactivate the metal-depleted PZAse in vitro. We use quantum mechanical calculations to investigate the Zn2+, Fe2+, and Mn2+ 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, Zn2+ and Mn2+ 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 Zn2+ 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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AU - Encomendero-Risco, Jimy J.

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