MUNI UNIVERSITY

FACULTY OF SCIENCE
DEPARTMENT OF CHEMISTRY
SOLID STATE CHEMISTRY
Assignment 1

Student Name: AZABO KENNEDY

Student Number: 2001200145

Metallothioneins (MTs)
Metallothioneins are proteins consisting of a single polypeptide chain of 61-62 amino acids
containing 20 cysteine residues which contain several bivalent cations (zinc, copper, cadmium,
and mercury) bound through metal thiolate linkages.
They are high inducible, low-molecular-weight protein that binds cadmium with high affinity
and is found in most tissues.
Metals and stress are the known inducers of MTS in earthworms.
It is found in bacteria, plants, invertebrates, and vertebrates.

Metallothionein structure
Based on the structural model, it can be assumed that the MT molecule is composed of two
binding domains, α and β, which are composed of cysteine clusters. Covalent binding of metal
atoms involve sulfhydryl cysteine residues. The N- terminal part of the peptide is designated as
β-domain has three binding sites for divalent ions, and the C- terminals part (the α – domain) has
the ability to bind four divalent metal ions.
The α-domain is closer to the C-terminal and is more stable while the other is a more reactive β-
domain, which is closer to the N-terminal.
The functional domains are linked with varying lengths of amino acid sequence, and these
linkers determine the structural stability of the metallothioneins.
Structure of Metallothionein
Functions of Metallothioneins

Protection against oxidative stress. Metallothioneins protect cells from exposure to oxidants
and electrophiles which react readily with sulfhydryl groups.
Metallo-homeostasis; Metallothioneins contains high levels of Sulphur which has mutual
affinity for metals making the binding for metals to metallothioneins thermodynamically stable.
Detoxification of metals; Metallothioneins play a role in protecting against cadmium toxicity
through interactions with cadmium metal.
Radical scavenging; a process by which a substance such as an antioxidant helps protect cells
from the damage caused by free radicals.
Metal ion transportation is the movement of ions across a membrane, passively through ion
channels or actively through ion pumps such as symporters and antiporters.
Maintenance of redox pool; it is by mobilization of metals by maintaining the reduced
(metallic) pool.
Protection; MTs have a high binding affinity to bivalent metal ions. A number of studies have
demonstrated the presence or enhanced synthesis of MT in rapidly proliferating normal cells,
regenerating cells and cancer cells. The studies have suggested a relationship between high
expression of MT protein and aggressive neoplastic cell growth. Due to their nucleophilicity,
MTs have been shown to protect cells against the cytotoxic effects of electrophilic anticancer
drugs. However, protection of cells by MT from the cytotoxic effect of agents such as 1-β-D-
arabinofuranosyl cytosine and nuclear factor DF-α must involve mechanisms other than simple
covalent binding.
Act as buffers; buffering against toxic heavy metals, Metallothioneins are resistant to heavy
metal toxicity and are able to knock out these metals.
Examples
⮚ Yeast ,Yeast which is basically found in the following
⮚ Saccharomyces cerevisiae - brewer’s yeast.
⮚ Neurospora crassa – red bread mold.
Cysteine

Oxidized
Iso forms of MTS
• The four isoforms are identified in mammals, three of which, MT-I, II, and III are found
in the central nervous system.
• The expression of MT-I and II is mainly localized in glias and is induced by exposure to
metals including Hg, Cd, Cu and zinc.
References
1. Mutation research/fundamental and molecular mechanisms of mutagenesis, 2001
2. Metalloenzyme.” Egyptian Journal of Medical Human Genetics, Elsevier.
3. Pernil R, Schleiff E. (2019 ) metallo protein in biology of Hetrocysts.
4. Strenkert D, Limso CA, Fatihi A, et al (2016) photosynthetic cofactor mechanism,
Royal Society of Chemistry