Hemerythrin is an
oligomerIn chemistry, an oligomer is a molecule that consists of a few monomer units , in contrast to a polymer that, at least in principle, consists of an unlimited number of monomers. Dimers, trimers, and tetramers are oligomers. Many oils are oligomeric, such as liquid paraffin...
ic
proteinProteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
responsible for
oxygenOxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
(O
2) transport in the marine invertebrate phyla of sipunculids, priapulids,
brachiopodBrachiopods are a phylum of marine animals that have hard "valves" on the upper and lower surfaces, unlike the left and right arrangement in bivalve molluscs. Brachiopod valves are hinged at the rear end, while the front can be opened for feeding or closed for protection...
s, and in a single
annelidThe annelids , formally called Annelida , are a large phylum of segmented worms, with over 17,000 modern species including ragworms, earthworms and leeches...
worm, magelona. Recently, hemerythrin was discovered in methanotrophic bacterium
Methylococcus capsulatusMethylococcus capsulatus is an obligately methanotrophic gram-negative, non-motile coccoid bacterium. M. capsulatus cells are encapsulated and tend to have a diplococcoid arrangement. In addition to methane, M. capsulatus is able to oxidize some organic hydrogen containing compounds such as...
.
Myohemerythrin is a
monomerA monomer is an atom or a small molecule that may bind chemically to other monomers to form a polymer; the term "monomeric protein" may also be used to describe one of the proteins making up a multiprotein complex...
ic O
2-binding protein found in the muscles of marine invertebrates. Hemerythrin and myohemerythrin are essentially colorless when deoxygenated, but turn a violet-pink in the oxygenated state.
Hemerythrin does
not, as the name might suggest, contain a
hemeA heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are...
. The names of the blood oxygen transporters
hemoglobinHemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
,
hemocyaninHemocyanins are respiratory proteins in the form of metalloproteins containing two copper atoms that reversibly bind a single oxygen molecule . Oxygenation causes a color change between the colorless Cu deoxygenated form and the blue Cu oxygenated form...
, hemerythrin and
vanabinsVanabins are a specific group of vanadium-binding metalloproteins. Vanabins are found almost exclusively in the blood cells, or vanadocytes of some ascidians and tunicates . The vanabins extracted from tunicate vanadocytes are often called hemovanadins...
, do not refer to the heme group (only found in globins), instead these names are derived from the Greek word for blood.
O2 binding mechanism
The mechanism of dioxygen binding is unusual. Most O
2 carriers operate via formation of
Dioxygen complexDioxygen complexes are coordination compounds that contain O2 as a ligand. The study of these compounds is inspired by oxygen-carrying proteins such as myoglobin, hemoglobin, hemerythrin, and hemocyanin. Several transition metals form complexes with O2, and many of these complexes form reversibly...
es, but hemerythrin holds the O
2 as a hydroperoxide. The site that binds O
2 consists of a pair of iron centres. The iron atoms are bound to the protein through the carboxylate side chains of a glutamate and aspartates as well as through five
histidineHistidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...
residues. Hemerythrin and myohemerythrin are often described according to oxidation and ligation states of the iron centre:
| Fe2+—OH—Fe2+ |
deoxy (reduced) |
| Fe2+—OH—Fe3+ |
semi-met |
| Fe3+—O—Fe3+—OOH- |
oxy (oxidized) |
| Fe3+—OH—Fe3+— (any other ligand) |
met (oxidized) |
The uptake of O
2 by hemerythrin is accompanied by two-electron oxidation of the di
ferrousFerrous , in chemistry, indicates a divalent iron compound , as opposed to ferric, which indicates a trivalent iron compound ....
centre to produce a hydroperoxide (OOH
-) complex. The binding of O
2 binding is roughly described in scheme:
Deoxyhemerythrin contains two high-spin ferrous ions bridged by
hydroxylA hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...
group (
A). One iron is hexacoordinate and another is pentacoordinate. A
hydroxylA hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...
group serves as a
bridging ligandA bridging ligand is a ligand that connects two or more atoms, usually metal ions. The ligand may be atomic or polyatomic. Virtually all complex organic compounds can serve as bridging ligands, so the term is usually restricted to small ligands such as pseudohalides or to ligands that are...
but also functions as a proton donor to the O
2 substrate. This proton-transfer result in the formation of a single oxygen atom (μ-oxo) bridge in oxy- and methemerythrin. O
2 binds to the pentacoordinate Fe
2+ centre at the vacant coordination site (
B). Then electrons are transferred from the ferrous ions to generate the binuclear ferric (Fe
3+,Fe
3+) centre with bound peroxide (
C).
Quaternary structure and cooperativity
Hemerythrin typically exists as a homooctamer or heterooctamer composed of α- and β-type subunits of 13-14 kDa each, although some species have dimeric, trimeric and tetrameric hemerythrins. Each subunit has a four-α-helix fold binding a binuclear iron centre. Because of its size hemerythrin is usually found in cells or "corpuscles" in the blood rather than free floating.
Unlike hemoglobin, most hemerythrins lack
cooperative bindingIn biochemistry, a macromolecule exhibits cooperative binding if its affinity for its ligand changes with the amount of ligand already bound.Cooperative binding is a special case of allostery. Cooperative binding requires that the macromolecule have more than one binding site, since cooperativity...
to oxygen, making it roughly 1/4 as efficient as hemoglobin. In some brachiopods though, hemerythrin shows cooperative binding of O
2. Cooperative binding is achieved by interactions between subunits: the oxygenation of one subunit increases the affinity of a second unit for oxygen.
Hemerythrin affinity for
carbon monoxideCarbon monoxide , also called carbonous oxide, is a colorless, odorless, and tasteless gas that is slightly lighter than air. It is highly toxic to humans and animals in higher quantities, although it is also produced in normal animal metabolism in low quantities, and is thought to have some normal...
(CO) is actually lower than its affinity for O
2, unlike hemoglobin which has a very high affinity for CO. Hemerythrin's low affinity for CO poisoning reflects the role of hydrogen-bonding in the binding binding O2, a pathway mode that is incompatible with CO complexes which usually do not engage in hydrogen bonding.
Hemerythrin/HHE cation-binding domain
The hemerythrin/HHE cation-binding
domainA protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...
occurs as a duplicated domain in hemerythrins, myohemerythrins and related proteins. This domain binds
ironIron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
in hemerythrin, but can bind other metals in related proteins, such as
cadmiumCadmium is a chemical element with the symbol Cd and atomic number 48. This soft, bluish-white metal is chemically similar to the two other stable metals in group 12, zinc and mercury. Similar to zinc, it prefers oxidation state +2 in most of its compounds and similar to mercury it shows a low...
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 oxideNitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...
, which suggests a different set-up for its metal ligands. A protein from
Cryptococcus neoformansCryptococcus neoformans is an encapsulated yeast that can live in both plants and animals. Its teleomorph is Filobasidiella neoformans, a filamentous fungus belonging to the class Tremellomycetes. It is often found in pigeon excrement....
(Filobasidiella neoformans) that contains haemerythrin/HHE cation-binding domains is also involved in nitric oxide response. A
Staphylococcus aureusStaphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
protein containing this domain, iron-sulfur cluster repair protein ScdA, has been noted to be important when the
organismIn biology, an organism is any contiguous living system . In at least some form, all organisms are capable of response to stimuli, reproduction, growth and development, and maintenance of homoeostasis as a stable whole.An organism may either be unicellular or, as in the case of humans, comprise...
switches to living in environments with low oxygen concentrations; perhaps this protein acts as an oxygen store or scavenger.
External links
- 1HMD - PDB
The Protein Data Bank is a repository for the 3-D structural data of large biological molecules, such as proteins and nucleic acids....
structure of deoxyhemerythrin Themiste dyscrita (sipunculid worm)
- 1HMO - PDB structure of oxyhemerythrin from Themiste dyscrita
- 2MHR - PDB structure of azido-met myohemerythrin from Themiste zostericola (sipunculid worm)
- IPR002063 - InterPro entry for hemerythrin