Hemocyanin

From Wikipedia, the free encyclopedia

Hemocyanin, copper containing domain

Single Oxygenated Functional Unit from the

hemocyanin of an octopus
Identifiers
Hemocyanin_M
Symbol
PF00372
Pfam
IPR000896
InterPro
PDOC00184
PROSITE
1lla
SCOP
1lla
SUPERFAMILY
[show]Available protein structures:

Hemocyanin, all-alpha domain

crystal structure of hexameric haemocyanin from

panulirus interruptus refined at 3.2 angstroms

resolution
Identifiers
Hemocyanin_N
Symbol
PF03722
Pfam
IPR005204
InterPro
PDOC00184
PROSITE
1lla
SCOP
1lla
SUPERFAMILY
[show]Available protein structures:

Hemocyanin, ig-like domain

crystallographic analysis of oxygenated and

deoxygenated states of arthropod hemocyanin shows
unusual differences
Identifiers
Hemocyanin_C
Symbol
PF03723
Pfam
IPR005203
InterPro
PDOC00184
PROSITE
1lla
SCOP
1lla
SUPERFAMILY
[show]Available protein structures:
Hemocyanins (also spelled haemocyanins) 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 (O2). They are second only to hemoglobin in frequency
of use as an oxygen transport molecule. Unlike the hemoglobin in red blood cells found in
vertebrates, hemocyanins are not bound to blood cells but are instead suspended directly in the
hemolymph. Oxygenation causes a color change between the colorless Cu(I) deoxygenated form
and the blue Cu(II) oxygenated form.

Contents
1 Species distribution
2 Structure and mechanism
3 Catalytic activity
4 Spectral properties
5 Antitumor effects
6 See also
7 References
8 Further reading
9 External links

Species distribution
Hemocyanins are found in two animal phyla, Mollusca and Arthropoda, but hemocyanins from
the two phyla are rather different. In both types, however, the copper sites are similar.
Hemocyanins are quite widespread among molluscs. A hemocyanin was first discovered in 1927
by Svedberg[1] from the snail Helix pomatia. Among arthropods, a hemocyanin was early
discovered in the horseshoe crab, Limulus polyphemus. Hemocyanins are well known among
crustaceans such as lobsters and crabs. More recently they have been found among land
arthropods such as the tarantula Eurypelma californicum,[2] the scorpion Pandinus imperator,[3]
and the centipede Scutigera coleoptrata. Arthropod hemocyanins must have originated early in
the evolutionary history of this phylum as they have been found from the class Onychophora.[4]
Hemocyanins seem to be rare among insects but are not completely absent.[5] Larval storage
proteins in many insects appear to be derived from hemocyanins.

Structure and mechanism

The underside of the carapace of a Cancer productus crab. The purple coloring is caused by
hemocyanin.
Although the respiratory function of hemocyanin is similar to that of hemoglobin, there are a
significant number of differences in its molecular structure and mechanism. Whereas
hemoglobin carries its iron atoms in porphyrin rings (heme groups), the copper atoms of
hemocyanin are bound as prosthetic groups coordinated by histidine residues. It has been noted
that species using hemocyanin for oxygen transportation include crustaceans living in cold

environments with low oxygen pressure. Under these circumstances hemoglobin oxygen
transportation is less efficient than hemocyanin oxygen transportation.[6] Nevertheless there are
also terrestrial arthropods using hemocyanin, notably spiders and scorpions, that live in warm
climates.
Most hemocyanins bind with oxygen non-cooperatively and are roughly one-fourth as efficient
as hemoglobin at transporting oxygen per amount of blood. Hemoglobin binds oxygen
cooperatively due to steric conformation changes in the protein complex, which increases
hemoglobin's affinity for oxygen when partially oxygenated. In some hemocyanins of horseshoe
crabs and some other species of arthropods, cooperative binding is observed, with Hill
coefficients of 1.6 - 3.0. Hill coefficients vary depending on species and laboratory measurement
settings. Hemoglobin, for comparison, has a Hill coefficient of usually 2.8 - 3.0. In these cases of
cooperative binding hemocyanin was arranged in protein sub-complexes of 6 subunits (hexamer)
each with one oxygen binding site; binding of oxygen on one unit in the complex would increase
the affinity of the neighboring units. Each hexamer complex was arranged together to form a
larger complex of dozens of hexamers. In one study, cooperative binding was found to be
dependent on hexamers being arranged together in the larger complex, suggesting cooperative
binding between hexamers. Hemocyanin oxygen-binding profile is also affected by dissolved salt
ion levels and pH.[7]
Hemocyanin is made of many individual subunit proteins, each of which contains two copper
atoms and can bind one oxygen molecule (O2). Each subunit weighs about 75 kilodaltons (kDa).
Subunits may be arranged in dimers or hexamers depending on species; the dimer or hexamer
complex is likewise arranged in chains or clusters with weights exceeding 1500 kDa. The
subunits are usually homogeneous, or heterogeneous with two variant subunit types. Because of
the large size of hemocyanin, it is usually found free-floating in the blood, unlike hemoglobin.[8]
Hexamers are characteristic of arthropod hemocyanins.[9] A hemocyanin of the tarantula
Eurypelma californicum[2] is made up of 4 hexamers or 24 pepide chains. A hemocyanin from
the house centipede Scutigera coleoptrata[10] is made up of 6 hexamers or 36 chains. Horseshoe
crabs have an 8-hexamer (i. e. 48-chain) hemocyanin. Simple hexamers are found in the spiny
lobster Panulirus interruptus and the isopod Bathynomus giganteus.[11] Peptide chains in
crustaceans are about 660 amino acid residues long, and in chelicerates they are about 625. In the
large complexes there is a variety of variant chains, all about the same length; pure components
do not usually self-assemble.

Catalytic activity
Hemocyanin is homologous to the phenol oxidases (e.g. tyrosinase) since both enzymes sharing
type 3 Cu active site coordination. Hemocyanin also exhibits phenol oxidase activity, but with
slowed kinetics from greater steric bulk at the active site. Partial denaturation actually improves
hemocyanins phenol oxidase activity by providing greater access to the active site.[12]

Spectral properties

Oxygen binding mode with respect to copper centers

Spectroscopy of oxyhemocyanin shows several salient features:[citation needed]
1.
2.
3.
4.

resonance Raman spectroscopy shows symmetric binding

UV-Vis spectroscopy shows strong absorbances at 350 and 580 nm.
OxyHc is EPR-silent indicating the absence of unpaired electrons
Infrared spectroscopy shows (O-O) of 755 cm-1

(1) rules out a mononuclear peroxo complex (2) does not match with the UV-Vis spectra of
mononuclear peroxo and Kenneth Karlin's trans-peroxo models.[13] (4) shows a considerably
weaker O-O bond compared with Karlin's trans-peroxo model.[13]
On the other hand, Nobumasa Kitajima's model shows (O-O) of 741 cm-1 and UV-Vis
absorbances at 349 and 551 nm, which agree with the experimental observations for oxyHc.[14]

Antitumor effects
The hemocyanin found in Concholepas concholepas blood has immunotherapeutic effects
against bladder and prostate cancer in murine models. Researchers in 2006 primed mice with C.
concholepas before implantation of bladder tumor (MBT-2) cells. Mice treated with C.
concholepas showed significant antitumor effects: prolonged survival, decreased tumor growth
and incidence, and lack of toxic effects.[15]