BMS3020 L2 Basic Metallo-Biology 29/10/18
BMS3020 CHRONIC DISEASE
LECTURE 2 – Basic Metallo-Biology
Uses of Metals in Biology
Metal ions like copper, iron and zinc are important in the diet to survive, but they can also cause
severe disease if their mechanisms within the body are unregulated.
- Around 50% of enzymes contain metal as a co-
factor, predicted on genome sequences
- Life would not exist without metals
- Organisms must acquire these essential metals
and ensure that the correct metal associates
with the correct protein
- This is a complex process which can lead to the
development of disease
1. Structural Function
- Example: Zinc finger containing enzymes
- Zinc binds to 2 cysteine and 2 histidine residues in a specific motif
which creates a finger
- The finger in turn can be a protein-protein or protein-DNA
interaction domain
- The function of the zinc is purely structural, to hold the protein
domain in the correct conformation for it to function
2. Active Site of Enzyme
- Metals can act as the catalytic centre of an enzyme
- Example: Aconitase - converts citrate to isocitrate in the
mitochondrion contains a cluster of four iron atoms
and four sulphur atoms (FeS cluster)
- One iron atom is exposed to the sulphur which is where
the citrate substrate binds (catalytic site)
- Enzymes in biology which are redox active (gain and lose electrons)
e.g. copper (Cu+ Cu2+ and iron (Fe2+ Fe3+)
- Example: Cytochrome C Oxidase – in the respiratory chain where
electrons are passed from copper centres to iron centres within
haem
Metal Selection through Evolution
Superoxide dismutase (SOD1) is an enzyme which breaks down potentially harmful oxygen
molecules in cells which can help to prevent tissue damage.
- In bacteria, e.g. Escherichia coli the enzyme contains iron within its active site
- Within eukaryotic organisms e.g. Saccharomyces cerevisiae and humans, SOD1 contains
copper even though the bacterial version can function well in yeast
- Both catalyse the same reaction, so why have they evolved to use different metals?
- Yeast mutant with SOD1 knockout, can be replaced with SODB – the bacterial SOD which still
functions quite well
1
BMS3020 CHRONIC DISEASE
LECTURE 2 – Basic Metallo-Biology
Uses of Metals in Biology
Metal ions like copper, iron and zinc are important in the diet to survive, but they can also cause
severe disease if their mechanisms within the body are unregulated.
- Around 50% of enzymes contain metal as a co-
factor, predicted on genome sequences
- Life would not exist without metals
- Organisms must acquire these essential metals
and ensure that the correct metal associates
with the correct protein
- This is a complex process which can lead to the
development of disease
1. Structural Function
- Example: Zinc finger containing enzymes
- Zinc binds to 2 cysteine and 2 histidine residues in a specific motif
which creates a finger
- The finger in turn can be a protein-protein or protein-DNA
interaction domain
- The function of the zinc is purely structural, to hold the protein
domain in the correct conformation for it to function
2. Active Site of Enzyme
- Metals can act as the catalytic centre of an enzyme
- Example: Aconitase - converts citrate to isocitrate in the
mitochondrion contains a cluster of four iron atoms
and four sulphur atoms (FeS cluster)
- One iron atom is exposed to the sulphur which is where
the citrate substrate binds (catalytic site)
- Enzymes in biology which are redox active (gain and lose electrons)
e.g. copper (Cu+ Cu2+ and iron (Fe2+ Fe3+)
- Example: Cytochrome C Oxidase – in the respiratory chain where
electrons are passed from copper centres to iron centres within
haem
Metal Selection through Evolution
Superoxide dismutase (SOD1) is an enzyme which breaks down potentially harmful oxygen
molecules in cells which can help to prevent tissue damage.
- In bacteria, e.g. Escherichia coli the enzyme contains iron within its active site
- Within eukaryotic organisms e.g. Saccharomyces cerevisiae and humans, SOD1 contains
copper even though the bacterial version can function well in yeast
- Both catalyse the same reaction, so why have they evolved to use different metals?
- Yeast mutant with SOD1 knockout, can be replaced with SODB – the bacterial SOD which still
functions quite well
1
