Estudos in vitro e de modelagem molecular in silico aplicados à interação entre a enzima delta-aminolevulinato desidratase e metais do grupo 10 (níquel, paládio e platina) e 11 (cobre, prata e ouro) da tabela periódica ; Studies in vitro and molecular modeling in silico applied to the interaction between enzyme deltaaminolevulinate dehydratase and metals group 10 (nickel, palladium and platinum) and 11 (copper, silver and gold) the periodic table

Mammalian δ- aminolevulinate dehydratase (δ-ALA-D) is a metalloenzyme, which requires Zn(II) and reduced thiol groups for maximal catalytic activity, and is an important molecular target for the widespread environmental toxic metals. The mechanism underlying the δ-ALA-D inhibition by elements of Group 10 nickel (NiCl2), palladium (PdCl2), platinum (PtCl2 and PtCl4) and 11 cupper (CuSO4), silver (AgNO3), glod (AuCl3) of periodic table has not yet been determined. The main objective of the present study was to characterize the molecular mechanism of δ-ALA-D inhibition caused by salts of elements of Group 10 and 11 using in vitro (δ-ALA-D activity in human erythrocytes) and in silico (by geometry optimization with the program MOPAC20122 - PM6 method). Our results showed that Ni(II) and Pd(II) caused only a small inhibition (~ 10%) in the δ-ALA-D enzyme activity, and this inhibition was blunted by Zn(II). Pt forms significantly inhibited the enzymatic activity of δ- ALA-D (75% and 44%, respectively), but this inhibition was attenuated by Zn (II) and DTT, indicating that when moved the element most light to the heavier component, tends to change inhibition in a competition for Zn (II) for the oxidation of thiols. In group 11, all metals inhibited δ-ALA-D, and in accordance with data in vitro and in silico the mechanism of inhibition seems to be related to the oxidation of thiol groups of the active site, while incubation with Zn (II) appears to block the inhibitory mechanism of the metals of the group 11 for protecting the active enzyme. ; A enzima δ-aminolevulinato desidratase humana (δ-ALA-D) é uma metaloenzima que requer grupos tióis reduzidos e o metal Zn(II) para a atividade catalítica máxima, sendo consequentemente um alvo molecular importante para os metais tóxicos ambientais. Sendo assim, este estudo teve como objetivo caracterizar o mecanismo molecular de interação dos sais dos elementos do Grupo 10 niquel (NiCl2), paládio (PdCl2), platina (PtCl2 e PtCl4) e 11 cobre (CuSO4), prata (AgNO3), ouro (AuCl3) com o ...