Metal-binding mechanisms in metallothioneins

Abstract

Metallothionein are small, cysteine-rich, metal-binding proteins that are found ubiquitously in nature. Most metallothioneins bind multiple metals in two well-defined metal-thiolate clusters. This perspective discusses the use of optical spectroscopy to study the metalation of metallothioneins and the emergence of electrospray ionization mass spectrometry as a means of studying the mechanism of metalation for metallothioneins. A brief history of past kinetic studies of cadmium metallothioneins and recent kinetic study advances for the arsenic metalation of metallothionein will be presented. Lastly, a possible functional role for the two-domain structure of metallothionein will be briefly discussed.

Evidence for operation of the direct zinc ligand exchange mechanism for trafficking, transport, and reactivity of zinc in mammalian cells

“…Mammalian MTs are small (6 –7 kDa) non-enzymatic proteins, which contain 20 cysteine sites and bind up to seven Zn atoms [9, 59-61]. The molecular size of MT is especially important for the delivery of Zn to organellar zinc reactive sites.…”

“…MT is comprised of two domains that form thermodynamically stable and kinetically labile complexes with zinc ions [59,62]. Cysteine residues are exposed at the surface of the protein, not buried within; which allows them to participate in rapid direct transfer of zinc in site-specific binding complexes formed between MT and small molecules or other proteins [9].…”

Biochemical and Molecular Basis of Arsenic Toxicity and Tolerance in Microbes and Plants

“…Therefore, systems evolved by primordial organisms to cope with it still exist in prokaryotes. Responses of microorganisms may include (1) extracellular sequestration [54], (2) minimizing the amount of arsenic that enters the cell, e.g., through increased specificity of phosphate uptake [55], (3) chelation mediated by glutathione, phytochelatin, and metallothionein [52,56,57], (4) reduction [49][50][51]58] followed by efflux [58] and methylation [59,60], and (5) oxidation [61,62] ( Figure 27-2). It has been proposed recently that arsenic can substitute for phosphorus in proteins and nucleic acids [53].…”

“…This is mediated by peptides or proteins containing thiol ligands, such as glutathione, phytochelatins, and metallothioneins [52,56,57]. This is mediated by peptides or proteins containing thiol ligands, such as glutathione, phytochelatins, and metallothioneins [52,56,57].…”

Metal binding novel flaxseed peptides (linusorbs)

“…LO binding to other metals is largely unexplored. The presence of methionine sulphur in LOs 1 – 5 may stabilise metal binding as observed with other sulphur containing proteins (Chan et al ., ; Ngu & Stillman, ). Tryptophan and proline containing orbitides with nitrogen heterocyclic structures may also stabilise bound metal states (Ananthanarayanan et al ., ; Ma et al ., ).…”