MUNI UNIVERSITY

FACULTY OF SCIENCE
DEPARTMENT OF CHEMISTRY
ORGANOMETALLIC AND BIOINORGANIC CHEMISTRY
Assignment 2

Student Name: AZABO KENNEDY

Student Number: 2001200145

Metalloenzymes

Metalloenzymes are enzymes that contain a tightly bound metal ion. This metal ion forms
coordinate covalent bonds with the amino acids of the enzyme or with a prosthetic group.
Further, it acts as a coenzyme and imparts the activity of the enzyme.

Metalloenzymes are enzymatic proteins in which a metal or metal ion is embedded in the cavity
of the enzyme and forms strong bonds with the donor atoms of the protein. The donor atoms of
the protein may be earlier soft base 1or hard base as O and N. In The similar way, the metals may
be either soft metals 2such as Cu2+, Mg2+, Cd2+ or hard metals such as Fe3+, Zn2+ etc.

The protein part is called an apoenzyme and a metal ion or complex metal ion is called a
prosthetic group.

Many enzymes require some non-protein compounds in order to perform their catalytic action.
These compounds are collectively known as cofactors.

1
Soft base or acid is the one with low charge to radius ratio.

2
Soft metal is the metal that can be cut, bent, without shattering. This is because of weak
intermolecular forces in them.
When considering the location of the metal ion in the enzyme, it usually occurs in a specific
region on the enzyme surface. Therefore, the ion does not disturb the binding of the substrate
with the active site. Sometimes, enzymes require more than one metal ion for its activity. In rare
occasions, they require two different metal ions as well. The most common metals that involve
this are Fe, Zn, Cu, and Mn. The metalloenzymes containing metal centers other than iron (non-
heme centers) are widespread in nature.

Examples of metalloenzymes.

● Carbonic anhydrase.

The carbonic anhydrases (or carbonate dehydratases) form a family of enzymes that catalyze the
interconversion between carbon dioxide and water and the dissociated ions of carbonic acid (i.e.
bicarbonate and hydrogen ions). The active site of most carbonic anhydrases contains a zinc
(Zn2+) ion. They are therefore classified as metalloenzymes.

Carbonic anhydrase plays an essential role in regulating the blood pH, which speeds up the

CO2 + H2O HCO3-+ H+

reaction to ensure the equilibrium balance is rapidly maintained. The equilibrium reaction is
influenced by the proportion of bicarbonate and H + to carbon dioxide. The HCO3- is a conjugate
base that neutralizes acids, and the H + is a conjugate acid that neutralizes bases by Acid-base
homeostasis.

It has tetrahedral geometry(due to its sp3 hybridisation of the carbon atoms) and carbonic
anhydrase has molecular mass of 30000g.

The structure of carbonic anhydrase.

 ● Catalase and peroxidase

Catalase and peroxidase are metalloenzymes that catalyze reactions of hydrogen peroxide. In
catalase, the enzymatic reaction is the disproportionation of hydrogen peroxide and the function
of the enzyme appears to be prevention of any buildup of that potentially dangerous oxidant.
They contain Fe3+ in the active site.

● Cytochrome c oxidase

Cytochromes are, in general, membrane-bound hemoproteins that contain heme groups and carry
out electron transport. A heme is a prosthetic group comprising an iron atom residing in the
center of a large heterocyclic organic molecule called a porphyrin. Hemoproteins are part of the
larger class of metalloproteins, which includes some complexes whose porphyrin prosthetic
group contains at its center a different metal atom than iron. The heme group is a highly-
conjugated ring system surrounding an iron ion, which readily interconverts between its primary
oxidation states. The iron ion interconverts between the Fe2+ (reduced) and Fe3+ (oxidized)
states in electron-transfer processes which is the primary role of cytochrome c oxidase.
Cytochromes are, thus, capable of performing oxidation and reduction.
Thermolysin: Thermolysin is a thermostable neutral metalloproteinase enzyme produced by the Gram-
positive bacteria. It requires one zinc ion for enzyme activity and four calcium ions for structural stability.
Thermolysin specifically catalyzes the hydrolysis of peptide bonds containing hydrophobic amino acids.
However, thermolysin is also widely used for peptide bond formation through the reverse reaction of
hydrolysis. In contrast to many proteins that undergo conformational changes upon heating and denaturation,
thermolysin does not undergo any major conformational changes until at least 70 °C.

Nitrile hydratase: Nitrile hydratase Nitrile hydratase, which catalyzes hydration of nitriles to
amides as shown below, is a key enzyme involved in the metabolism of the toxic compounds.
This enzyme is also industrially used in the kiloton-scale production of acrylamide and
nicotinamide from the corresponding nitriles. The cobalt ions are tightly bound to the enzymes in
their active site and are not liberated by dialysis. The enzymes have a maximum absorption at
410 nm and do not show corrin absorbance in the visible spectrum.

Reference:

1. Metalloenzyme.” Egyptian Journal of Medical Human Genetics, Elsevier. Available here

2. Pernil R, Schleiff E. (2019 ) metallo protein in biology of Hetrocysts.
3. Strenkert D, Limso CA, Fatihi A, et al (2016) photosynthetic cofactor mechanism, Royal
Society of Chemistry
4. Metalloprotein.” Wikipedia, Wikimedia Foundation, 23 July 2018.