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Two Distinct Thermodynamic Gradients for Cellular Metalation of Vitamin B12 (2023)
Journal Article
Young, T. R., Deery, E., Foster, A. W., Martini, M. A., Osman, D., Warren, M. J., & Robinson, N. J. (2023). Two Distinct Thermodynamic Gradients for Cellular Metalation of Vitamin B12. JACS Au, 3(5), 1264-1534. https://doi.org/10.1021/jacsau.3c00119

The acquisition of CoII by the corrin component of vitamin B12 follows one of two distinct pathways, referred to as early or late CoII insertion. The late insertion pathway exploits a CoII metallochaperone (CobW) from the COG0523 family of G3E GTPase... Read More about Two Distinct Thermodynamic Gradients for Cellular Metalation of Vitamin B12.

Metalation calculators for E. coli strain JM109 (DE3): Aerobic, anaerobic and hydrogen peroxide exposed cells cultured in LB media (2022)
Journal Article
Foster, A. W., Clough, S. E., Aki, Z., Young, T. R., Clarke, A. R., & Robinson, N. J. (2022). Metalation calculators for E. coli strain JM109 (DE3): Aerobic, anaerobic and hydrogen peroxide exposed cells cultured in LB media. Metallomics, 14(9), https://doi.org/10.1093/mtomcs/mfac058

Three Web-based calculators, and three analogous spreadsheets, have been generated that predict in vivo metal occupancies of proteins based on known metal affinities. The calculations exploit estimates of the availabilities of the labile buffered poo... Read More about Metalation calculators for E. coli strain JM109 (DE3): Aerobic, anaerobic and hydrogen peroxide exposed cells cultured in LB media.

Insights into the antibacterial mechanism of action of chelating agents by selective deprivation of iron, manganese and zinc (2021)
Journal Article
Paterson, J. R., Beecroft, M. S., Mulla, R. S., Osman, D., Reeder, N. L., Caserta, J. A., …Sharples, G. J. (2022). Insights into the antibacterial mechanism of action of chelating agents by selective deprivation of iron, manganese and zinc. Applied and Environmental Microbiology, https://doi.org/10.1128/aem.01641-21

Bacterial growth and proliferation can be restricted by limiting the availability of metal ions in their environment. Humans sequester iron, manganese and zinc to help prevent infection by pathogens, a system termed nutritional immunity. Commercially... Read More about Insights into the antibacterial mechanism of action of chelating agents by selective deprivation of iron, manganese and zinc.

Acquisition of ionic copper by the bacterial outer membrane protein OprC through a novel binding site (2021)
Journal Article
Bhamidimarri, S. P., Young, T. R., Shanmugam, M., Soderholm, S., Baslé, A., Bumann, D., & van den Berg, B. (2021). Acquisition of ionic copper by the bacterial outer membrane protein OprC through a novel binding site. PLoS Biology, 19(11), Article e3001446. https://doi.org/10.1371/journal.pbio.3001446

Copper, while toxic in excess, is an essential micronutrient in all kingdoms of life due to its essential role in the structure and function of many proteins. Proteins mediating ionic copper import have been characterised in detail for eukaryotes, bu... Read More about Acquisition of ionic copper by the bacterial outer membrane protein OprC through a novel binding site.

Protein metalation in biology (2021)
Journal Article
Foster, A. W., Young, T. R., Chivers, P. T., & Robinson, N. J. (2022). Protein metalation in biology. Current Opinion in Chemical Biology, 66, Article 102095. https://doi.org/10.1016/j.cbpa.2021.102095

Inorganic metals supplement the chemical repertoire of organic molecules, especially proteins. This requires the correct metals to associate with proteins at metalation. Protein mismetalation typically occurs when excesses of unbound metals compete f... Read More about Protein metalation in biology.

Principles and practice of determining metal–protein affinities (2021)
Journal Article
Young, T. R., & Xiao, Z. (2021). Principles and practice of determining metal–protein affinities. Biochemical Journal, 478(5), 1085-1116. https://doi.org/10.1042/bcj20200838

Metal ions play many critical roles in biology, as structural and catalytic cofactors, and as cell regulatory and signalling elements. The metal–protein affinity, expressed conveniently by the metal dissociation constant, KD, describes the thermodyna... Read More about Principles and practice of determining metal–protein affinities.

Calculating metalation in cells reveals CobW acquires Co(II) for vitamin B12 biosynthesis while related proteins prefer Zn(II) (2021)
Journal Article
Young, T., Martini, M., Foster, A., Glasfeld, A., Osman, D., Morton, R., …Robinson, N. (2021). Calculating metalation in cells reveals CobW acquires Co(II) for vitamin B12 biosynthesis while related proteins prefer Zn(II). Nature Communications, 12, Article 1195. https://doi.org/10.1038/s41467-021-21479-8

Protein metal-occupancy (metalation) in vivo has been elusive. To address this challenge, the available free energies of metals have recently been determined from the responses of metal sensors. Here, we use these free energy values to develop a meta... Read More about Calculating metalation in cells reveals CobW acquires Co(II) for vitamin B12 biosynthesis while related proteins prefer Zn(II).

The Human Amyloid Precursor Protein Binds Copper Ions Dominated by a Picomolar Affinity Site in the Helix-Rich E2 Domain (2018)
Journal Article
Young, T. R., Pukala, T. L., Cappai, R., Wedd, A. G., & Xiao, Z. (2018). The Human Amyloid Precursor Protein Binds Copper Ions Dominated by a Picomolar Affinity Site in the Helix-Rich E2 Domain. Biochemistry, 57(28), 4165-4176. https://doi.org/10.1021/acs.biochem.8b00572

A manifestation of Alzheimer’s disease (AD) is the aggregation in the brain of amyloid β (Aβ) peptides derived from the amyloid precursor protein (APP). APP has been linked to modulation of normal copper homeostasis, while dysregulation of Aβ product... Read More about The Human Amyloid Precursor Protein Binds Copper Ions Dominated by a Picomolar Affinity Site in the Helix-Rich E2 Domain.

Evaluation of Cu(I) binding to the E2 domain of the amyloid precursor protein – a lesson in quantification of metal binding to proteins via ligand competition (2017)
Journal Article
Young, T. R., Wedd, A. G., & Xiao, Z. (2018). Evaluation of Cu(I) binding to the E2 domain of the amyloid precursor protein – a lesson in quantification of metal binding to proteins via ligand competition. Metallomics, 10(1), 108-119. https://doi.org/10.1039/c7mt00291b

The extracellular domain E2 of the amyloid precursor protein (APP) features a His-rich metal-binding site (denoted as the M1 site). In conjunction with surrounding basic residues, the site participates in interactions with components of the extracell... Read More about Evaluation of Cu(I) binding to the E2 domain of the amyloid precursor protein – a lesson in quantification of metal binding to proteins via ligand competition.

Copper binding and redox chemistry of the Aβ16 peptide and its variants: insights into determinants of copper-dependent reactivity (2017)
Journal Article
Yako, N., Young, T. R., Cottam Jones, J. M., Hutton, C. A., Wedd, A. G., & Xiao, Z. (2017). Copper binding and redox chemistry of the Aβ16 peptide and its variants: insights into determinants of copper-dependent reactivity. Metallomics, 9(3), 278-291. https://doi.org/10.1039/c6mt00299d

The metal-binding sites of Aβ peptides are dictated primarily by the coordination preferences of the metal ion. Consequently, Cu(I) is typically bound with two His ligands in a linear mode while Cu(II) forms a pseudo-square planar stereochemistry wit... Read More about Copper binding and redox chemistry of the Aβ16 peptide and its variants: insights into determinants of copper-dependent reactivity.

CopC Protein from Pseudomonas fluorescens SBW25 Features a Conserved Novel High-Affinity Cu(II) Binding Site (2015)
Journal Article
Wijekoon, C. J., Young, T. R., Wedd, A. G., & Xiao, Z. (2015). CopC Protein from Pseudomonas fluorescens SBW25 Features a Conserved Novel High-Affinity Cu(II) Binding Site. Inorganic Chemistry, 54(6), 2950-2959. https://doi.org/10.1021/acs.inorgchem.5b00031

Copper homeostasis in the bacterium Pseudomonas fluorescens SBW25 appears to be mediated mainly via chromosomal cue and cop systems. Under elevated copper levels that induce stress, the cue system is activated for expression of a P1B-type ATPase to r... Read More about CopC Protein from Pseudomonas fluorescens SBW25 Features a Conserved Novel High-Affinity Cu(II) Binding Site.

A set of robust fluorescent peptide probes for quantification of Cu(II) binding affinities in the micromolar to femtomolar range (2015)
Journal Article
Young, T. R., Wijekoon, C. J., Spyrou, B., Donnelly, P. S., Wedd, A. G., & Xiao, Z. (2015). A set of robust fluorescent peptide probes for quantification of Cu(II) binding affinities in the micromolar to femtomolar range. Metallomics, 7(3), 567-578. https://doi.org/10.1039/c4mt00301b

Reliable quantification of copper binding affinities and identification of the binding sites provide a molecular basis for an understanding of the nutritional roles and toxic effects of copper ions. Sets of chromophoric probes are now available that... Read More about A set of robust fluorescent peptide probes for quantification of Cu(II) binding affinities in the micromolar to femtomolar range.

An integrated study of the affinities of the Aβ16 peptide for Cu(I) and Cu(II): implications for the catalytic production of reactive oxygen species (2014)
Journal Article
Young, T. R., Kirchner, A., Wedd, A. G., & Xiao, Z. (2014). An integrated study of the affinities of the Aβ16 peptide for Cu(I) and Cu(II): implications for the catalytic production of reactive oxygen species. Metallomics, 6(3), 505-517. https://doi.org/10.1039/c4mt00001c

A new fluorescent probe Aβ16wwa based upon the Aβ16 peptide has been developed with two orders of magnitude greater fluorescence intensity for sensitive detection of interactions with Cu(II). In combination with the Cu(I) probe Ferene S, it is confir... Read More about An integrated study of the affinities of the Aβ16 peptide for Cu(I) and Cu(II): implications for the catalytic production of reactive oxygen species.

Quantification of copper binding to amyloid precursor protein domain 2 and its Caenorhabditis elegans ortholog. Implications for biological function (2013)
Journal Article
Leong, S. L., Young, T. R., Barnham, K. J., Wedd, A. G., Hinds, M. G., Xiao, Z., & Cappai, R. (2014). Quantification of copper binding to amyloid precursor protein domain 2 and its Caenorhabditis elegans ortholog. Implications for biological function. Metallomics, 6(1), 105-116. https://doi.org/10.1039/c3mt00258f

Aberrant regulation of transition metals and the resultant disregulation of neuronal reactive oxygen species (ROS) are considered significant in the etiology of Alzheimer's disease (AD). We determined the solution structure of the D2 domain of APL-1... Read More about Quantification of copper binding to amyloid precursor protein domain 2 and its Caenorhabditis elegans ortholog. Implications for biological function.