Editing Hemocyanin (section)

== 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 [[iron]] atoms in [[porphyrin]] rings ([[heme]] groups), the [[copper]] atoms of hemocyanin are bound as [[prosthetic group]]s coordinated by [[histidine]] residues. Each hemocyanin monomer holds a pair of copper(I) cations in place via interactions with the [[imidazole]] rings of six histidine residues.<ref name="Rannulu, N. S.">{{cite journal | vauthors = Rannulu NS, Rodgers MT | title = Solvation of copper ions by imidazole: structures and sequential binding energies of Cu+(imidazole)x, x = 1-4. Competition between ion solvation and hydrogen bonding | journal = Physical Chemistry Chemical Physics | volume = 7 | issue = 5 | pages = 1014–1025 | date = March 2005 | pmid = 19791394 | doi = 10.1039/b418141g | bibcode = 2005PCCP....7.1014R }}</ref> 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.<ref name="pmid22791630">{{cite journal | vauthors = Strobel A, Hu MY, Gutowska MA, Lieb B, Lucassen M, Melzner F, Pörtner HO, Mark FC | display-authors = 6 | title = Influence of temperature, hypercapnia, and development on the relative expression of different hemocyanin isoforms in the common cuttlefish Sepia officinalis | journal = Journal of Experimental Zoology. Part A, Ecological Genetics and Physiology | volume = 317 | issue = 8 | pages = 511–523 | date = December 2012 | pmid = 22791630 | doi = 10.1002/jez.1743 | url = https://epic.awi.de/id/eprint/31021/2/Strobel_etal_2012a.pdf }}</ref> 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.<ref>{{cite journal | vauthors = Sterner R, Vogl T, Hinz HJ, Penz F, Hoff R, Föll R, Decker H | title = Extreme thermostability of tarantula hemocyanin | journal = FEBS Letters | volume = 364 | issue = 1 | pages = 9–12 | date = May 1995 | pmid = 7750550 | doi = 10.1016/0014-5793(95)00341-6 | doi-access =  }}</ref>

Most hemocyanins bind with oxygen non-[[Cooperative binding|cooperatively]] and are roughly one-fourth as efficient as hemoglobin at transporting oxygen per amount of blood. Hemoglobin binds oxygen cooperatively due to steric [[protein folding|conformation]] changes in the [[protein complex]], which increases hemoglobin's affinity for oxygen when partially oxygenated. In some hemocyanins of [[horseshoe crab]]s and some other species of [[arthropods]], cooperative binding is observed, with [[Hill coefficient]]s 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]].<ref name="pmid9187351">{{cite journal | vauthors = Perton FG, Beintema JJ, Decker H | title = Influence of antibody binding on oxygen binding behavior of Panulirus interruptus hemocyanin | journal = FEBS Letters | volume = 408 | issue = 2 | pages = 124–126 | date = May 1997 | pmid = 9187351 | doi = 10.1016/S0014-5793(97)00269-X | doi-access =  }}</ref>

Hemocyanin is made of many individual subunit proteins, each of which contains two [[copper]] atoms and can bind one oxygen molecule (O<sub>2</sub>). Each subunit weighs about 75 [[Dalton (unit)|kilodaltons]] (kDa). Subunits may be arranged in [[protein dimer|dimer]]s or [[hexamer]]s depending on species; the dimer or hexamer complex is likewise arranged in chains or clusters with weights exceeding 1500 kDa. The subunits are usually [[wiktionary:Homogeneous|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.<ref name="pmid1126935">{{cite journal | vauthors = Waxman L | title = The structure of arthropod and mollusc hemocyanins | journal = The Journal of Biological Chemistry | volume = 250 | issue = 10 | pages = 3796–3806 | date = May 1975 | pmid = 1126935 | doi = 10.1016/S0021-9258(19)41469-5 | doi-access = free }}</ref>

[[File:Molluscan hemocyanin (4YD9).png|thumb|center|upright=3|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 Cu<sub>2</sub>O<sub>2</sub> binding site.<ref>{{Cite journal |last1=Gai |first1=Zuoqi |last2=Matsuno |first2=Asuka |last3=Kato |first3=Koji |last4=Kato |first4=Sanae |last5=Khan |first5=Md Rafiqul Islam |last6=Shimizu |first6=Takeshi |last7=Yoshioka |first7=Takeya |last8=Kato |first8=Yuki |last9=Kishimura |first9=Hideki |last10=Kanno |first10=Gaku |last11=Miyabe |first11=Yoshikatsu |last12=Terada |first12=Tohru |last13=Tanaka |first13=Yoshikazu |last14=Yao |first14=Min |date=2015 |title=Crystal Structure of the 3.8-MDa Respiratory Supermolecule Hemocyanin at 3.0 Å Resolution |journal=Structure |language=en |volume=23 |issue=12 |pages=2204–2212 |doi=10.1016/j.str.2015.09.008|doi-access=free |pmid=26602184 }}</ref> {{PDB|4YD9}}]]

Hexamers are characteristic of arthropod hemocyanins.<ref name="pmid8561049">{{cite book|title=Advances in Protein Chemistry |vauthors=van Holde KE, Miller KI|publisher=Academic Press |year=1995 |isbn=978-0-12-034247-1| veditors = Anfinsen CB, Richards FM, Edsall JT, Eisenberg DS |volume=47 |pages=1–81 |chapter=Hemocyanins |doi=10.1016/S0065-3233(08)60545-8|pmid=8561049 }}</ref> A hemocyanin of the tarantula ''Eurypelma californicum''<ref name="Voit_2000"/> is made up of 4 hexamers or 24 peptide chains. A hemocyanin from the house centipede ''Scutigera coleoptrata''<ref name="pmid12823556">{{cite journal | vauthors = Kusche K, Hembach A, Hagner-Holler S, Gebauer W, Burmester T | title = Complete subunit sequences, structure and evolution of the 6 x 6-mer hemocyanin from the common house centipede, Scutigera coleoptrata | journal = European Journal of Biochemistry | volume = 270 | issue = 13 | pages = 2860–2868 | date = July 2003 | pmid = 12823556 | doi = 10.1046/j.1432-1033.2003.03664.x | doi-access = free }}</ref> 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''.<ref name=pmid8561049/> 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.{{citation needed|date=February 2017}}