Unraveling the metallo-mystery pair: the role of MbnP and MbnH in bacterial copper transport

Project: Research project

Project Details

Description

Copper (Cu) is an essential redox active metal with a vital role in metabolic functions. However, misregulation in humans is linked to a variety of diseases, including Wilson disease. Promising treatment options f or conditions of Cu overload include the use of synthetic or natural product chelators that tightly bind Cu allowing f or excess metal removal. One family of natural product chelators that has received significant attention are ribosomally synthesized, post translationally modifed peptides found in aerobicmethane-oxidizing bacteria. These natural products, called methanobactins (Mbns) are produced and secreted under Cu-limited conditions and bind Cu with extremely high af f inities. While Cu acquisition by Mbns is relatively well understood, the mechanism by which these compounds release Cu f or use in the cellis unknown.
Two copper-regulated genes, mbnP and mbnH, are f ound both within Mbn operons and elsewhere in the genome, typically neighboring genes encoding homologs of the Mbn transporter MbnT. MbnH belongs to the bacterial diheme cytochrome cperoxidase (bCcP)/MauG superfamily, whereas MbnP contains no previously identified domains. Bioinformatics analysis and preliminary data suggest that these two proteins play a role in microbial copper homeostasis. In the proposed project, the f unction and structure of MbnP and MbnH will be investigated by both in vitro and in vivo approaches and use biochemical and bipphysical techniques. This research will provide new insights into microbial copper handling as well as elucidate new functions and mechanisms of diheme enzymes.
StatusActive
Effective start/end date8/1/207/31/23

Funding

  • Life Sciences Research Foundation (Princeton, NJ) (Agmt. 07/08/20)

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