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37  structures 3149  species 1  interaction 6352  sequences 141  architectures

Family: Hemerythrin (PF01814)

Summary: Hemerythrin HHE cation binding domain

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Hemerythrin Edit Wikipedia article

Single Oxygenated Hemerythrin protein
Trimeric Hemerythrin Protein Complex

Hemerythrin (also spelled haemerythrin; from Greek words αίμα = blood and ερυθρός = red) is an oligomeric protein responsible for oxygen (O2) transport in the marine invertebrate phyla of sipunculids, priapulids, brachiopods, and in a single annelid worm genus, Magelona. Myohemerythrin is a monomeric O2-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 heme. The names of the blood oxygen transporters hemoglobin, hemocyanin, hemerythrin, 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 O2 carriers operate via formation of dioxygen complexes, but hemerythrin holds the O2 as a hydroperoxide. The site that binds O2 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 histidine 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 O2 by hemerythrin is accompanied by two-electron oxidation of the diferrous centre to produce a hydroperoxide (OOH-) complex. The binding of O2 is roughly described in this diagram:

Active site of hemerythrin before and after oxygenation.

Deoxyhemerythrin contains two high-spin ferrous ions bridged by hydroxyl group (A). One iron is hexacoordinate and another is pentacoordinate. A hydroxyl group serves as a bridging ligand but also functions as a proton donor to the O2 substrate. This proton-transfer result in the formation of a single oxygen atom (μ-oxo) bridge in oxy- and methemerythrin. O2 binds to the pentacoordinate Fe2+ centre at the vacant coordination site (B). Then electrons are transferred from the ferrous ions to generate the binuclear ferric (Fe3+,Fe3+) centre with bound peroxide (C).[1][2]

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 binding to oxygen, making it roughly 1/4 as efficient as hemoglobin. In some brachiopods though, hemerythrin shows cooperative binding of O2. 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 monoxide (CO) is actually lower than its affinity for O2, 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 of O2, a pathway mode that is incompatible with CO complexes which usually do not engage in hydrogen bonding.

Hemerythrin/HHE cation-binding domain

Hemerythrin HHE cation binding domain
PDB 2igf EBI.jpg
crystal structures of an antibody to a peptide and its complex with peptide antigen at 2.8 angstroms
Identifiers
Symbol Hemerythrin
Pfam PF01814
InterPro IPR012312
PROSITE PDOC00476
SCOP 2hmq
SUPERFAMILY 2hmq

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.[3] 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.[4]

References

  1. ^ D. M. Kurtz, Jr. "Dioxygen-binding Proteins" in Comprehensive Coordination Chemistry II 2003, Volume 8, Pages 229-260. doi:10.1016/B0-08-043748-6/08171-8
  2. ^ Friesner, R. A., M.-H. Baik, B. F. Gherman, V. Guallar, M. Wirstam, R. B. Murphy, and S. J. Lippard, 2003, How iron-containing proteins control dioxygen chemistry: a detailed atomic level description via accurate quantum chemical and mixed quantum mechanics/molecular mechanics calculations: Coord. Chem. Rev., v. 238-239, p. 267-290.
  3. ^ Chow ED, Liu OW, O'Brien S, Madhani HD (September 2007). "Exploration of whole-genome responses of the human AIDS-associated yeast pathogen Cryptococcus neoformans var grubii: nitric oxide stress and body temperature". Curr. Genet. 52 (3–4): 137–48. doi:10.1007/s00294-007-0147-9. PMID 17661046. 
  4. ^ Overton TW, Justino MC, Li Y, Baptista JM, Melo AM, Cole JA et al. (2008). "Widespread Distribution in Pathogenic Bacteria of Di-Iron Proteins That Repair Oxidative and Nitrosative Damage to Iron-Sulfur Centers". J Bacteriol 190 (6): 2004–13. doi:10.1128/JB.01733-07. PMC 2258886. PMID 18203837. 

Further reading

  • Karlsen, O.A., Ramsevik, L., Bruseth, L.J., Larsen, Ø., Brenner, A., Berven, F.S., Jensen, H.B. and Lillehaug, J.R. (2005). "Characterization of a prokaryotic haemerythrin from the methanotrophic bacterium Methylococcus capsulatus (Bath)". FEBS J. 272 (10): 2428–2440. doi:10.1111/j.1742-4658.2005.04663.x. PMID 15885093. 
  • Stenkamp, R.E. (1994). "Dioxygen and hemerythrin". Chem. Rev. 94 (3): 715–726. doi:10.1021/cr00027a008. 

External links

  • 1HMD - PDB 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

This article incorporates text from the public domain Pfam and InterPro IPR012312

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Hemerythrin HHE cation binding domain Provide feedback

Iteration of the HHE family ([2]) found it to be related to Hemerythrin. It also demonstrated that what has been described as a single domain ([1]) in fact consists of two cation binding domains. Members of this family occur all across nature and are involved in a variety of processes. For instance, in Nereis diversicolor P80255 binds Cadmium so as to protect the organism from toxicity ([3]). However Hemerythrin is classically described as Oxygen-binding through two attached Fe2+ ions. And the bacterial Q7WX96 is a regulator of response to NO, which suggests yet another set-up for its metal ligands ([4]). In Staphylococcus aureus P72360 has been noted to be important when the organism switches to living in environments with low oxygen concentrations ([4]); perhaps this protein acts as an oxygen store or scavenger.

Literature references

  1. Stenkamp RE, Sieker LC, Jensen LH, McQueen JE Jr; , Biochemistry 1978;17:2499-2504.: Structure of methemerythrin at 2.8-Angstrom resolution: computer graphics fit of an averaged electron density map. PUBMED:678527 EPMC:678527

  2. Yeats C, Bentley S, Bateman A; , BMC Microbiol 2003;3:3-3.: New Knowledge from Old: In silico discovery of novel protein domains in Streptomyces coelicolor. PUBMED:12625841 EPMC:12625841

  3. Martins LJ, Hill CP, Ellis WR Jr; , Biochemistry 1997;36:7044-7049.: Structures of wild-type chloromet and L103N hydroxomet Themiste zostericola myohemerythrins at 1.8 A resolution. PUBMED:9188702 EPMC:9188702

  4. Throup JP, Zappacosta F, Lunsford RD, Annan RS, Carr SA, Lonsdale JT, Bryant AP, McDevitt D, Rosenberg M, Burnham MK; , Biochemistry 2001;40:10392-10401.: The srhSR gene pair from Staphylococcus aureus: genomic and proteomic approaches to the identification and characterization of gene function. PUBMED:11513618 EPMC:11513618


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR012312

This entry represents a haemerythrin/HHE cation-binding domain that occurs as a duplicated domain [PUBMED:12625841] in haemerythrins, myohemerythrins and related proteins. This domain binds iron in haemerythrin, but can bind other metals in related proteins, such as cadmium in a Nereis diversicolor protein (SWISSPROT) [PUBMED:12743530]. A bacterial protein, SWISSPROT, is a regulator of response to NO, 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 NO response [PUBMED:17661046]. A Staphylococcus aureus protein (SWISSPROT) has been noted to be important when the organism switches to living in environments with low oxygen concentrations [PUBMED:11513618]; perhaps this protein acts as an oxygen store or scavenger.

Domain organisation

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  Seed
(189)
Full
(6352)
Representative proteomes NCBI
(4919)
Meta
(320)
RP15
(719)
RP35
(1432)
RP55
(1824)
RP75
(2104)
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  Seed
(189)
Full
(6352)
Representative proteomes NCBI
(4919)
Meta
(320)
RP15
(719)
RP35
(1432)
RP55
(1824)
RP75
(2104)
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Seed source: Yeats C
Previous IDs: none
Type: Domain
Author: Bateman A, Yeats C
Number in seed: 189
Number in full: 6352
Average length of the domain: 127.90 aa
Average identity of full alignment: 17 %
Average coverage of the sequence by the domain: 51.44 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.0 25.0
Trusted cut-off 25.0 25.0
Noise cut-off 24.9 24.9
Model length: 133
Family (HMM) version: 18
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Species distribution

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Interactions

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Hemerythrin

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Hemerythrin domain has been found. There are 37 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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