Environmental Science and Pollution Research

, Volume 25, Issue 30, pp 30557–30566 | Cite as

Interaction of metals from group 10 (Ni, Pd, and Pt) and 11 (Cu, Ag, and Au) with human blood δ-ALA-D: in vitro and in silico studies

  • Cláudia Vargas Klimaczewski
  • Pablo Andrei NogaraEmail author
  • Nilda Vargas Barbosa
  • João Batista Teixeira da RochaEmail author
Research Article


Mammalian δ-aminolevulinate dehydratase (δ-ALA-D) is a metalloenzyme, which requires Zn(II) and reduced thiol groups for catalytic activity, and is an important molecular target for the widespread environmental toxic metals. The δ-ALA-D inhibition mechanism by metals of Group 10 (Ni, Pd, and Pt) and 11 (Cu, Ag, and Au) of the periodic table has not yet been determined. The objective of this study was to characterize the molecular mechanism of δ-ALA-D inhibition caused by the elements of groups 10 and 11 using in vitro (δ-ALA-D activity from human erythrocytes) and in silico (docking simulations) methods. Our results showed that Ni(II) and Pd(II) caused a small inhibition (~ 10%) of the δ-ALA-D. Pt(II) and Pt(IV) significantly inhibited the enzyme (75% and 44%, respectively), but this inhibition was attenuated by Zn(II) and dithiothreitol (DTT). In group 11, all metals inhibited δ-ALA-D with great potency (~ 70–90%). In the presence of Zn(II) and DTT, the enzyme activity was restored to the control levels. The in silico molecular docking data suggest that the coordination of the ions Pt(II), Pt(IV), Cu(II), Ag(I), and Au(III) with thiolates groups from C135 and C143 residues from the δ-ALA-D active site are crucial to the enzyme inhibition. The results indicate that a possible mechanism of inhibition of δ-ALA-D by these metals may involve the replacement of the Zn(II) from the active site and/or the cysteinyl residue oxidation.


Porphobilinogen synthase Nickel Palladium Platinum Copper Silver Gold Docking 


Funding information

This study is financially supported by FAPERGS/CNPq 12/2014-PRONEX: no. 16/2551-0000, CAPES/PROEX (23038.005848/2018-31; 0737/2018), and INCT-EN: for Cerebral Diseases, Excitotoxicity, and Neuroprotection.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

11356_2018_3048_MOESM1_ESM.docx (364 kb)
ESM 1 (DOCX 363 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Programa de Pós Graduação em Ciências Biológicas: Bioquímica ToxicológicaUniversidade Federal de Santa Maria (UFSM)Santa MariaBrazil
  2. 2.Centro de Ciências Naturais e ExatasPrograma de Pós-graduação em Bioquímica ToxicológicaSanta MariaBrazil
  3. 3.Departamento de Bioquímica e Biologia MolecularUniversidade Federal de Santa Maria (UFSM)Santa MariaBrazil

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