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.

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 p

SUBMITTER: Salazar-Salinas K 

PROVIDER: S-EPMC4514207 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature