ORCID Profile
0000-0002-1121-7761
Current Organisation
Institut de Química Computacional i Catàlisi, Universitat de Girona
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Publisher: Springer Science and Business Media LLC
Date: 23-11-2020
DOI: 10.1038/S41598-020-76178-Z
Abstract: Heavy metal sequestration from industrial wastes and agricultural soils is a long-standing challenge. This is more critical for copper since copper pollution is hazardous both for the environment and for human health. In this study, we applied an integrated approach of Darwin’s theory of natural selection with bacterial genetic engineering to generate a biological system with an application for the accumulation of Cu 2+ ions. A library of recombinant non-pathogenic Escherichia coli strains was engineered to express seven potential Cu 2+ binding peptides encoded by a ‘synthetic degenerate’ DNA motif and fused to Maltose Binding Protein (MBP). Most of these peptide-MBP chimeras conferred tolerance to high concentrations of copper sulphate, and in certain cases in the order of 160-fold higher than the recognised EC 50 toxic levels of copper in soils. UV–Vis spectroscopic analysis indicated a molar ratio of peptide-copper complexes, while a combination of bioinformatics-based structure modelling, Cu 2+ ion docking, and MD simulations of peptide-MBP chimeras corroborated the extent of Cu 2+ binding among the peptides. Further, in silico analysis predicted the peptides possessed binding affinity toward a broad range of alent metal ions. Thus, we report on an efficient, cost-effective, and environment-friendly prototype biological system that is potentially capable of copper bioaccumulation, and which could easily be adapted for the removal of other hazardous heavy metals or the bio-mining of rare metals.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 15-07-2022
Abstract: Zinc is essential for all organisms and yet detrimental at elevated levels. Hence, homeostasis of this metal is tightly regulated. The Zrt/Irt-like proteins (ZIPs) represent the only zinc importers in metazoans. Mutations in human ZIPs cause serious disorders, but the mechanism by which ZIPs transfer zinc remains elusive. Hitherto, structural information is only available for a model member, BbZIP, and as a single, ion-bound conformation, precluding mechanistic insights. Here, we elucidate an inward-open metal-free BbZIP structure, differing substantially in the relative positions of the two separate domains of ZIPs. With accompanying coevolutional analyses, mutagenesis, and uptake assays, the data point to an elevator-type transport mechanism, likely shared within the ZIP family, unifying earlier functional data. Moreover, the structure reveals a previously unknown ninth transmembrane segment that is important for activity in vivo. Our findings outline the mechanistic principles governing ZIP-protein transport and enhance the molecular understanding of ZIP-related disorders.
Publisher: Cold Spring Harbor Laboratory
Date: 05-09-2021
DOI: 10.1101/2021.09.01.458532
Abstract: Transition metals, such as zinc, are essential micronutrients in all organisms, but also highly toxic in excessive amounts. Heavy-metal transporting P-type (P IB ) ATPases are crucial for homeostasis, conferring cellular detoxification and redistribution through transport of these ions across cellular membranes. No structural information is available for the P IB-4 -ATPases, the subclass with the broadest cargo scope, and hence even their topology remains elusive. Here we present structures and complementary functional analyses of an archetypal P IB-4 -ATPases, sCoaT from Sulfitobacter sp. NAS14-1. The data disclose the architecture, devoid of classical so-called heavy metal binding domains, and provides fundamentally new insights into the mechanism and ersity of heavy-metal transporters. We reveal several novel P-type ATPase features, including a dual role in heavy-metal release, and as an internal counter ion, of an invariant, central histidine. We also establish that the turn-over of P IB -ATPases is potassium independent, contrasting to many other P-type ATPases. Combined with new inhibitory compounds, our results open up for efforts in e.g. drug discovery, since P IB-4 -ATPases function as virulence factors in many pathogens.
Location: Spain
Location: Taiwan, Province of China
No related grants have been discovered for Dhani Ram Mahato.