Universidad Peruana Cayetano Heredia

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

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dc.contributor.author Salazar-Salinas, Karim
dc.contributor.author Baldera-Aguayo, Pedro A.
dc.contributor.author Encomendero-Risco, Jimy J.
dc.contributor.author Orihuela, Melvin
dc.contributor.author Sheen Cortavarria, Patricia
dc.contributor.author Seminario, Jorge M.
dc.contributor.author Zimic-Peralta, Mirko Juan
dc.date.accessioned 2020-06-10T18:12:14Z
dc.date.available 2020-06-10T18:12:14Z
dc.date.issued 2014
dc.identifier.uri https://hdl.handle.net/20.500.12866/8064
dc.description.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 horizontal lineNepsilon (His) bond from the M. tuberculosis MCS is the best IR probe to metal complexation. en_US
dc.language.iso eng
dc.publisher American Chemical Society
dc.relation.ispartofseries Journal of Physical Chemistry. B
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Quantum Theory en_US
dc.subject Amidohydrolases/chemistry/metabolism en_US
dc.subject Coordination Complexes/chemistry/metabolism en_US
dc.subject Metals/pharmacology en_US
dc.subject Models, Molecular en_US
dc.subject Mycobacterium tuberculosis/enzymology en_US
dc.subject Protein Conformation en_US
dc.subject Pyrazinamide/chemistry/metabolism en_US
dc.subject Spectrophotometry, Infrared/methods en_US
dc.subject Vibration en_US
dc.subject Water/chemistry/metabolism en_US
dc.title 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 en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1021/jp504096d
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#1.04.03
dc.relation.issn 1520-5207


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