KNOW MORE

Weblinks
 https://en.wikipedia.org/wiki/Hemerythrin
 https://en.wikipedia.org/wiki/Hemocyanin
 http://www.sciencedirect.com/science/article/pii/S1570963913000836
 https://en.wikipedia.org/wiki/Hemoglobin
 http://pubs.acs.org/doi/abs/10.1021/bi00825a014
 http://chemed.chem.purdue.edu/genchem/topicreview/bp/1biochem/
blood3.html

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 Suggested Readings

Hamdbook on metalloproteins
By Ivano Bertini, Astrid Sigel, Helmut Sigel

Hemoglobin: Structure, function,

evolution and pathology

By Dickerson, Richard E.

Handbook of Metalloproteins: 2 Volume

Set

By Albrecht Messerschmidt, Robert

Huber, Thomas Poulos, Karl Wieghardt

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 Glossary

Arthropod- aAn arthropod is an invertebrate animal having an exoskeleton (external skeleton),

asegmented body, and jointed appendages. Arthropods form the phylum Arthropoda and include the
insects, arachnids, myriapods and crustaceans.

Hemerythrin- It is a non-heme iron protein used by two phyla of marine invertebrates (sipunculids
and brachiopods) for oxygen transfer and storage. It differs from other oxygen binding proteins
(haemoglobin and hemocyanin) both in the polypeptide chain and in the metal complex used to
reversibly bind oxygen.

Hemocyanin- Hemocyanins are proteins that transport oxygen throughout the bodies of some
invertebrate animals. These metalloproteins contain two copper atoms that reversibly bind a single
oxygen molecule . They are second only to haemoglobin in frequency of use as an oxygen transport
molecule.

Hemoglobin- It is the protein molecule in red blood cells that carries oxygen from the lungs to the
body’s tissues and returns carbon dioxide from the tissues back to the lungs. Hemoglobin is made up
of four protein molecules (globulin chains) that are connected together.

Invertebrates- Invertebrates are animals that neither possess nor develop a vertebral column,
derived from the notochord. This includes all animals apart from the subphylum Vertebrata. Familiar
examples of invertebrates include insects, crabs, lobsters and their kin, snails, clams, octopuses and
their kin, starfish and worms.

Metalloproteins- Metalloprotein is a generic term for a protein that contains a metal ion cofactor. A
large number of all proteins are part of this category.

Myoglobin- Myoglobin is an iron- and oxygen-binding protein found in the muscle tissue of
vertebrates in general and in almost all mammals. It is related to haemoglobin which is the iron- and
oxygen-binding protein in blood specifically in the red blood cells.

Oligomer- Oligomer is a molecular complex that consists of a few monomer units, in contrast to a
polymer where the number of monomers is, in principle, not limited. Dimers, trimers and tetramers,
for instance, oligomers composed of two, three and four monomers, respectively.

Oxygenation- Oxygenation is the process of oxygen diffusing passively from the alveolus to the
pulmonary capillary, where it binds to hemoglobin in red blood cells or dissolves into the plasma.

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 P

Porphyrins- Porphyrins are a group of heterocyclic macrocycle organic compounds, composed of

four modified pyrrole subunitsinterconnected at their α carbon atoms via methane bridges (=CH-).
The parent porphyrin is porphin and substituted porphines are called porphyrins.

Do you know?

Hemerythrin/HHE cation-binding domain

The hemerythrin/HHE cation-binding domain occurs as a duplicated domain in hemerythrins,

myohemerythrins and related proteins. This domain binds iron in hemerythrin, but can bind other
metals in related proteins, such as cadmium in the Nereis diversicolor hemerythrin. It is also found in
the NorA protein from Cupriavidus necator, this protein is a regulator of response to nitric oxide,
which suggests a different set-up for its metal ligands. A protein from Cryptococcus
neoformans(Filobasidiella neoformans) that contains haemerythrin/HHE cation-binding domains is
also involved in nitric oxide response. A Staphylococcus aureus protein containing this domain, iron-
sulfur cluster repair protein ScdA, has been noted to be important when the organism switches to
living in environments with low oxygen concentrations; perhaps this protein acts as an oxygen store
or scavenger.

Keyhole limpet hemocyanin

Keyhole limpet hemocyanin (KLH) is a large, multisubunit, oxygen-

carrying, metalloprotein that is found in the hemolymph of the giant keyhole
limpet, Megathura crenulata, a species of keyhole limpet that lives off the coast of California,
from Monterey Bay to Isla Asuncionoff Baja California.

Protein properties

There are two keyhole limpet hemocyanin genes, termed KLH1 and KLH2 which share around 60%
identity at the protein level. Both encode large glycosylated proteins consisting of around 3400 amino
acids and a molecular weight of around 390,000 Daltons, excluding the glycosylation. The protein
oligomerises to form a barrel shaped didecameric complex which is composed of 20 monomers. Each
domain of a KLH subunit contains two copper atomsthat together bind a single oxygen molecule (O2).
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 When oxygen is bound to hemocyanin, the molecule takes on a
distinctive transparent, opalescent blue color, due to the Cu2+ state of the copper. In the absence of
oxygen, the bound copper is found as Cu1+ and hemocyanin is colorless. The KLH protein is potently
immunogenic, but does not cause an adverse immune response in humans. It is therefore highly prized
as a vaccine carrier protein. Because of its size and glycosylation, KLH protein cannot be reproduced
synthetically; it is available only as a purified biological product from the keyhole limpet Megathura
crenulata.

Use in cancer therapy

KLH is being tested in a variety of cancer vaccines, including non-Hodgkins lymphoma,

cutaneousmelanoma, breast and bladder cancer. These vaccines contain specific tumor-associated
antigens conjugated to KLH to stimulate anti-tumor immune responses which can destroy tumor
cells.The rapidly growing interest in therapeutic vaccines (i.e. active immunotherapies) for cancer and
the documented efficacy of KLH as a superior carrier protein for cancer vaccines are creating a
significant biopharmaceutical market for KLH formulations.

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