Hemocyanin

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Hemocyanin, copper containing domain
SCOP2
1lla / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PDB1oxy :110-373 1nol :110-373 1lla :110-373

1ll1 :110-373 1hc1A:136-393 1hcyD:136-393 1hc6B:136-393 1hc4C:136-393 1hc3C:136-393

1hc5C:136-393 1hc2C:136-393
Hemocyanin, all-alpha domain
SCOP2
1lla / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
Hemocyanin, ig-like domain
SCOP2
1lla / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

Hemocyanins (also spelled haemocyanins and abbreviated Hc) are

vertebrates, hemocyanins are not confined in 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.[1]

Species distribution

Hemocyanin was first discovered in

Arthropoda including cephalopods and crustaceans and utilized by some land arthropods such as the tarantula Eurypelma californicum,[3] the emperor scorpion,[4] and the centipede Scutigera coleoptrata. Also, larval storage proteins in many insects appear to be derived from hemocyanins.[5]

The hemocyanin superfamily

The arthropod hemocyanin

dipteran) hexamerin receptors.[6]

Phenoloxidase are copper containing tyrosinases. These proteins are involved in the process of sclerotization of arthropod cuticle, in wound healing, and humoral immune defense. Phenoloxidase is synthesized by zymogens and are activated by cleaving an N-terminal peptide.[7]

Hexamerins are storage proteins commonly found in insects. These proteins are synthesized by the larval fat body and are associated with molting cycles or nutritional conditions.[8]

Pseudohemocyanin and cryptocyanins genetic sequences are closely related to hemocyanins in crustaceans. These proteins have a similar structure and function, but lack the copper binding sites.[9]

The evolutionary changes within the phylogeny of the hemocyanin superfamily are closely related to the emergence of these different proteins in various species. The understanding of proteins within this superfamily would not be well understood without the extensive studies of hemocyanin in arthropods.[10]

Structure and mechanism

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

crustaceans living in cold environments with low oxygen pressure. Under these circumstances hemoglobin oxygen transportation is less efficient than hemocyanin oxygen transportation.[12] Nevertheless, there are also terrestrial arthropods using hemocyanin, notably spiders and scorpions, that live in warm climates. The molecule is conformationally stable and fully functioning at temperatures up to 90 degrees C.[13]

Most hemocyanins bind with oxygen non-

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.[14]

Hemocyanin is made of many individual subunit proteins, each of which contains two

heterogeneous with two variant subunit types. Because of the large size of hemocyanin, it is usually found free-floating in the blood, unlike hemoglobin.[15]

The 3.8 MDa structure of molluscan Japanese flying squid hemocyanin. It is a homodecamer of five dimers arranged into a 31 nm diameter cylinder. Each monomer has a string of eight individual subunits each with a Cu2O2 binding site.[16] PDB: 4YD9​

Hexamers are characteristic of arthropod hemocyanins.

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.[citation needed
]

Catalytic activity

A hemocyanin active site in the absence of O2 (each Cu center is a cation, charges not shown).
O2-bound form of a hemocyanin active site (the Cu2 center is a dication, charge not shown).

Hemocyanin is homologous to the phenol oxidases (e.g.

phenol oxidase activity, but with slowed kinetics from greater steric bulk at the active site. Partial denaturation actually improves hemocyanin's phenol oxidase activity by providing greater access to the active site.[1][19]

Spectral properties

The underside of the carapace of a red rock crab (Cancer productus). The purple coloring is caused by hemocyanin.

Spectroscopy of oxyhemocyanin shows several salient features:[21]

  1. Resonance Raman spectroscopy shows that O2 is bound in a symmetric environment (ν(O-O) is not IR-allowed).
  2. OxyHc is EPR-silent indicating the absence of unpaired electrons
  3. Infrared spectroscopy shows ν(O-O) of 755 cm−1

Much work has been devoted to preparing synthetic analogues of the active site of hemocyanin.[21] One such model, which features a pair of copper centers bridged side-on by peroxo ligand, shows ν(O-O) at 741 cm−1 and a UV-Vis spectrum with absorbances at 349 and 551 nm. Both of these measurements agree with the experimental observations for oxyHc.[22] The Cu-Cu separation in the model complex is 3.56 Å, that of oxyhemocyanin is ca. 3.6 Å (deoxyHc: ca. 4.6 Å).[22][23][24]

Anticancer effects

The hemocyanin found in the blood of the Chilean abalone,

tumor (MBT-2) cells. Mice treated with C. concholepas hemocyanin showed antitumor effects: prolonged survival, decreased tumor growth and incidence, and lack of toxic effects and may have a potential use in future immunotherapy for superficial bladder cancer.[25]

Keyhole limpet hemocyanin (KLH) is an immune stimulant derived from circulating glycoproteins of the marine mollusk Megathura crenulata. KLH has been shown to be a significant treatment against the proliferations of breast cancer, pancreas cancer, and prostate cancer cells when delivered in vitro. Keyhole limpet hemocyanin inhibits growth of human Barrett's esophageal cancer through both apoptic and nonapoptic mechanisms of cell death.[26]

Case studies: environmental impact on hemocyanin levels

A 2003 study of the effect of culture conditions of blood metabolites and hemocyanin of the white shrimp

Litopenaeus vannamei found that the levels of hemocyanin, oxyhemocyanin in particular, are affected by the diet. The study compared oxyhemocyanin levels in the blood of white shrimp housed in an indoor pond with a commercial diet with that of white shrimp housed in an outdoor pond with a more readily available protein source (natural live food) as well. Oxyhemocyanin and blood glucose levels were higher in shrimp housed in outdoor ponds. It was also found that blood metabolite levels tended to be lower in low activity level species, such as crabs, lobsters, and the indoor shrimp when compared to the outdoor shrimp. This correlation is possibly indicative of the morphological and physiological evolution of crustaceans. The levels of these blood proteins and metabolites appear to be dependent on energetic demands and availability of those energy sources.[27]

See also

References

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Further reading

External links

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