# Hemoprotein

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Protein containing a heme prosthetic group

Binding of oxygen to a heme prosthetic group, which would be part of a hemoprotein.

A **hemeprotein** (or **haemprotein**; also **hemoprotein** or **haemoprotein**), or [heme](/source/Heme) protein, is a [protein](/source/Protein) that contains a [heme](/source/Heme) [prosthetic group](/source/Prosthetic_group).[1] They are a very large class of [metalloproteins](/source/Metalloprotein). The heme group confers functionality, which can include [oxygen carrying](/source/Oxygen-carrying_protein), oxygen reduction, electron transfer, and other processes. Heme is [bound](/source/Chemical_bond) to the protein either [covalently](/source/Covalent_bond) or noncovalently or both.[2]

The heme consists of iron cation bound at the center of the [conjugate base](/source/Conjugate_base) of the [porphyrin](/source/Porphyrin), as well as other [ligands](/source/Ligand) attached to the "axial sites" of the iron. The porphyrin ring is a planar dianionic, tetradentate ligand. The iron is typically Fe2+ or Fe3+. One or two ligands are attached at the axial sites. The porphyrin ring has four nitrogen atoms that bind to the iron, leaving two other coordination positions of the iron available for bonding to the histidine of the protein and a divalent atom.[2]

Hemeproteins probably evolved to incorporate the iron atom contained within the protoporphyrin IX ring of heme into proteins. As it makes hemeproteins responsive to molecules that can bind divalent iron, this strategy has been maintained throughout evolution as it plays crucial physiological functions. The serum iron pool maintains iron in soluble form, making it more accessible for cells.[3] Oxygen (O2), nitric oxide (NO), carbon monoxide (CO) and [hydrogen sulfide](/source/Hydrogen_sulfide) (H2S) bind to the iron atom in heme proteins. Once bound to the prosthetic heme groups, these molecules can modulate the activity/function of those hemeproteins, affording signal transduction. Therefore, when produced in biologic systems (cells), these gaseous molecules are referred to as gasotransmitters.

A [model](/source/Space-filling_model) of the Fe-[protoporphyrin IX](/source/Protoporphyrin_IX) subunit of the [Heme B](/source/Heme_B) cofactor.

Because of their diverse biological functions and widespread abundance, hemeproteins are among the most studied [biomolecules](/source/Biomolecule).[4] Data on heme protein structure and function has been aggregated into The Heme Protein Database (HPD), a secondary database to the [Protein Data Bank](/source/Protein_Data_Bank).[5]

## Roles

Hemeproteins have diverse biological functions including [oxygen transport](/source/Oxygen_transport), which is completed via hemeproteins including [hemoglobin](/source/Hemoglobin), [hemocyanin](/source/Hemocyanin),[6] [myoglobin](/source/Myoglobin), [neuroglobin](/source/Neuroglobin), [cytoglobin](/source/Cytoglobin), and [leghemoglobin](/source/Leghemoglobin).[7]

Some hemeproteins—[cytochrome P450s](/source/Cytochrome_P450), [cytochrome c oxidase](/source/Cytochrome_c_oxidase), [ligninases](/source/Ligninase), [catalase](/source/Catalase), and [peroxidases](/source/Peroxidase)—are enzymes. They often activate O2 for oxidation or hydroxylation.

Hemeproteins also enable [electron transfer](/source/Electron_transfer) as they form part of the [electron transport chain](/source/Electron_transport_chain). [Cytochrome a](/source/Cytochrome_c_oxidase), [cytochrome b](/source/Cytochrome_b), and [cytochrome c](/source/Cytochrome_c) have such electron transfer functions. It is now known that cytochrome a and cytochrome a3 make up one protein and was deemed the name cytochrome aa3.[8] The [sensory system](/source/Sensory_system) also relies on some hemeproteins including [FixL](https://en.wikipedia.org/w/index.php?title=FixL&action=edit&redlink=1), an oxygen sensor, [CooA](/source/CooA), a carbon monoxide sensor, and [soluble guanylyl cyclase](/source/Soluble_guanylyl_cyclase).

## Hemoglobin and myoglobin

Hemoglobin and myoglobin are examples of hemeproteins that respectively transport and store of oxygen in mammals and in some fish.[9] Hemoglobin is a [quaternary protein](/source/Protein_quaternary_structure) that occurs in the red blood cell, whereas, myoglobin is a [tertiary protein](/source/Protein_tertiary_structure) found in the muscle cells of mammals. Although they might differ in location and size, their function are similar. Being hemeproteins, they both contain a heme prosthetic group.

His-F8 of the myoglobin, also known as the proximal [histidine](/source/Histidine), is covalently bonded to the 5th coordination position of the iron. Oxygen interacts with the distal His by way of a hydrogen bond, not a covalent one. It binds to the 6th coordination position of the iron, His-E7 of the myoglobin binds to the oxygen that is now covalently bonded to the iron. The same is true for hemoglobin; however, being a protein with four [subunits](/source/Protein_subunit), hemoglobin contains four heme units in total, allowing four oxygen molecules in total to bind to the protein.

Myoglobin and hemoglobin are [globular proteins](/source/Globular_protein) that serve to bind and deliver oxygen using a prosthetic group. These globins dramatically improve the concentration of molecular oxygen that can be carried in the biological fluids of vertebrates and some invertebrates.

Differences occur in ligand binding and [allosteric regulation](/source/Allosteric_regulation).

### Myoglobin

Myoglobin is found in vertebrate muscle cells and is a water-soluble globular protein.[10] [Muscle cells](/source/Muscle_cell), when put into action, can quickly require a large amount of oxygen for respiration due to their energy requirements. Therefore, muscle cells use myoglobin to accelerate oxygen diffusion and act as localized oxygen reserves for times of intense respiration. Myoglobin also stores the required amount of oxygen and makes it available for the muscle cell mitochondria.

### Hemoglobin

In vertebrates, hemoglobin is found in the [cytosol](/source/Cytosol) of red blood cells. Hemoglobin is sometimes referred to as the oxygen transport protein, in order to contrast it with myoglobin, which is stationary.

In vertebrates, oxygen is taken into the body by the tissues of the lungs, and passed to the red blood cells in the bloodstream where it's used in aerobic metabolic pathways.[10] Oxygen is then distributed to all of the tissues in the body and offloaded from the red blood cells to respiring cells. The hemoglobin then picks up carbon dioxide to be returned to the lungs. Thus, hemoglobin binds and off-loads both oxygen and carbon dioxide at the appropriate tissues, serving to deliver the oxygen needed for cellular metabolism and removing the resulting waste product, CO2.

### Neuroglobin

Found in neurons, [neuroglobin](/source/Neuroglobin) is responsible for driving nitric oxide to promote neuron cell survival[11] Neuroglobin is believed to increase the oxygen supply for neurons, sustaining ATP production, but they also function as storage proteins.[12]

### Peroxidases and catalases

Almost all human [peroxidases](/source/Peroxidase) are hemoproteins, except glutathione peroxidase. They use hydrogen peroxide as a substrate. Metalloenzymes catalyze reactions using peroxide as an oxidant.[13] [Catalases](/source/Catalase) are hemoproteins responsible for the catalysis of converting hydrogen peroxide into water and oxygen.[14] They are made up of 4 subunits, each subunit having a Fe3+ heme group. They have an average molecular weight of ~240,000 g/mol.

[Haloperoxidases](/source/Haloperoxidase) involved in the [innate immune system](/source/Innate_immune_system) also contain a heme prosthetic group.

### Electron transport chain and other redox catalysts

[Cytochromes](/source/Cytochromes), [cytochrome c oxidase](/source/Cytochrome_c_oxidase), and [coenzyme Q – cytochrome c reductase](/source/Coenzyme_Q_%E2%80%93_cytochrome_c_reductase) are heme-containing proteins or protein subunits embedded in the inner membrane of mitochondria which play an essential role in [cellular respiration](/source/Cellular_respiration).

[Sulfite oxidase](/source/Sulfite_oxidase), a [molybdenum](/source/Molybdenum)-dependent cytochrome, oxidizes sulfite to sulfate.

### Nitric oxide synthase

Main article: [Nitric oxide synthase](/source/Nitric_oxide_synthase)

## Designed heme proteins

 Pincer-1:[15] A designed heme-binding peptide adopting an all-beta secondary structure.  ABOVE: Topological representation of Pincer-1 showing the secondary structure and designed interacting residues.  BELOW: All-atom 3-dimensional model of Pincer-1. This model was partially confirmed using [NMR](/source/Nuclear_Magnetic_Resonance).

Due to the diverse functions of the heme molecule: as an electron transporter, an oxygen carrier, and as an enzyme cofactor, heme binding proteins have consistently attracted the attention of protein designers. Initial design attempts focused on α-helical heme binding proteins, in part, due to the relative simplicity of designing self-assembling helical bundles. Heme binding sites were designed inside the inter-helical hydrophobic grooves. Examples of such designs include:

- Helichrome[16][17]

- Globin-1[18]

- Cy-AA-EK[19]

- Peptides IIa/IId[20]

- α2[21]

- Transmembrane helical designs[22][23][24]

Later design attempts focused on creating functional heme binding helical bundles, such as:

- [Oxidoreductases](/source/Oxidoreductase)[25][26]

- Peroxidases[27][28]

- Electron transport proteins[29]

- Oxygen transport proteins[30]

- Photosensitive proteins[25]

Design techniques have matured to such an extent that it is now possible to generate entire libraries of heme binding helical proteins.[31]

Recent design attempts have focused on creating all-beta heme binding proteins, whose novel topology is very rare in nature. Such designs include:

- Pincer-1[15]

- [β-hairpin](/source/%CE%92-hairpin) peptides[32]

- β-sheet miniproteins[33]

- Multi-stranded β-sheet peptides[34]

Some methodologies attempt to incorporate cofactors into the hemoproteins who typically endure harsh conditions. In order to incorporate a synthetic cofactor, what must first occur is the denaturing of the holoprotein to remove the heme. The apoprotein is then rebuilt with the cofactor.[35]

## References

1. **[^](#cite_ref-1)** ["Heme Prosthetic Group Definition"](http://earth.callutheran.edu/Academic_Programs/Departments/BioDev/omm/catalase/frames/hemetx.htm#:~:text=Heme%20group:%20A%20prosthetic%20group,propionate%20side%20chains%20are%20attached.). *earth.callutheran.edu*. Retrieved 2023-04-27.

1. ^ [***a***](#cite_ref-Lehn_2-0) [***b***](#cite_ref-Lehn_2-1) Nelson DL, Cox MN (2000). *Lehninger, Principles of Biochemistry* (3rd ed.). New Yorkm: Worth Publishing. [ISBN](/source/ISBN_(identifier)) [1-57259-153-6](https://en.wikipedia.org/wiki/Special:BookSources/1-57259-153-6).

1. **[^](#cite_ref-3)** Frazer, David M.; Anderson, Gregory J. (March 2014). ["The regulation of iron transport: The Regulation of Iron Transport"](https://onlinelibrary.wiley.com/doi/10.1002/biof.1148). *BioFactors*. **40** (2): 206–214. [doi](/source/Doi_(identifier)):[10.1002/biof.1148](https://doi.org/10.1002%2Fbiof.1148). [PMID](/source/PMID_(identifier)) [24132807](https://pubmed.ncbi.nlm.nih.gov/24132807). [S2CID](/source/S2CID_(identifier)) [2998785](https://api.semanticscholar.org/CorpusID:2998785).

1. **[^](#cite_ref-4)** Reedy CJ, Elvekrog MM, Gibney BR (January 2008). ["Development of a heme protein structure-electrochemical function database"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2238922). *Nucleic Acids Research*. **36** (Database issue): D307–D313. [doi](/source/Doi_(identifier)):[10.1093/nar/gkm814](https://doi.org/10.1093%2Fnar%2Fgkm814). [PMC](/source/PMC_(identifier)) [2238922](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2238922). [PMID](/source/PMID_(identifier)) [17933771](https://pubmed.ncbi.nlm.nih.gov/17933771).

1. **[^](#cite_ref-database_5-0)** Gibney BR. ["Heme Protein Database"](http://hemeprotein.info/heme.php). Brooklyn, NY: Brooklyn College.

1. **[^](#cite_ref-6)** ["hemoproteins - Humpath.com - Human pathology"](https://web.archive.org/web/20230427032941/https://www.humpath.com/spip.php?article14129). *www.humpath.com*. Archived from [the original](https://www.humpath.com/spip.php?article14129) on 2023-04-27. Retrieved 2023-04-27.

1. **[^](#cite_ref-7)** Lippard J, Berg JM (1994). *Principles of Bioinorganic Chemistry*. Mill Valley, CA: University Science Books. [ISBN](/source/ISBN_(identifier)) [0-935702-73-3](https://en.wikipedia.org/wiki/Special:BookSources/0-935702-73-3).

1. **[^](#cite_ref-8)** Mahinthichaichan, Paween; Gennis, Robert B.; Tajkhorshid, Emad (2018-04-10). ["Cytochrome aa 3 Oxygen Reductase Utilizes the Tunnel Observed in the Crystal Structures To Deliver O 2 for Catalysis"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5936630). *Biochemistry*. **57** (14): 2150–2161. [doi](/source/Doi_(identifier)):[10.1021/acs.biochem.7b01194](https://doi.org/10.1021%2Facs.biochem.7b01194). [ISSN](/source/ISSN_(identifier)) [0006-2960](https://search.worldcat.org/issn/0006-2960). [PMC](/source/PMC_(identifier)) [5936630](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5936630). [PMID](/source/PMID_(identifier)) [29546752](https://pubmed.ncbi.nlm.nih.gov/29546752).

1. **[^](#cite_ref-9)** Gerber, Lucie; Clow, Kathy A.; Driedzic, William R.; Gamperl, Anthony K. (July 2021). ["The Relationship between Myoglobin, Aerobic Capacity, Nitric Oxide Synthase Activity and Mitochondrial Function in Fish Hearts"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301165). *Antioxidants*. **10** (7): 1072. [doi](/source/Doi_(identifier)):[10.3390/antiox10071072](https://doi.org/10.3390%2Fantiox10071072). [ISSN](/source/ISSN_(identifier)) [2076-3921](https://search.worldcat.org/issn/2076-3921). [PMC](/source/PMC_(identifier)) [8301165](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301165). [PMID](/source/PMID_(identifier)) [34356305](https://pubmed.ncbi.nlm.nih.gov/34356305).

1. ^ [***a***](#cite_ref-accesspharmacy.mhmedical.com_10-0) [***b***](#cite_ref-accesspharmacy.mhmedical.com_10-1) ["Hemoglobin and Myoglobin | Integrative Medical Biochemistry Examination and Board Review | AccessPharmacy | McGraw Hill Medical"](https://accesspharmacy.mhmedical.com/content.aspx?bookid=1696&sectionid=111398218#:~:text=Hemoglobin%20is%20a%20heterotetrameric%20oxygen,intracellular%20storage%20site%20for%20oxygen.). *accesspharmacy.mhmedical.com*. Retrieved 2023-04-27.

1. **[^](#cite_ref-11)** DellaValle, Brian; Hempel, Casper; Kurtzhals, Jørgen A. L.; Penkowa, Milena (2010-08-01). ["In vivo expression of neuroglobin in reactive astrocytes during neuropathology in murine models of traumatic brain injury, cerebral malaria, and autoimmune encephalitis: Neuroglobin in Reactive Astrogliosis"](https://onlinelibrary.wiley.com/doi/10.1002/glia.21002). *Glia*. **58** (10): 1220–1227. [doi](/source/Doi_(identifier)):[10.1002/glia.21002](https://doi.org/10.1002%2Fglia.21002). [PMID](/source/PMID_(identifier)) [20544857](https://pubmed.ncbi.nlm.nih.gov/20544857). [S2CID](/source/S2CID_(identifier)) [8563830](https://api.semanticscholar.org/CorpusID:8563830).

1. **[^](#cite_ref-12)** Burmester, Thorsten; Hankeln, Thomas (June 2004). ["Neuroglobin: A Respiratory Protein of the Nervous System"](https://www.physiology.org/doi/10.1152/nips.01513.2003). *Physiology*. **19** (3): 110–113. [doi](/source/Doi_(identifier)):[10.1152/nips.01513.2003](https://doi.org/10.1152%2Fnips.01513.2003). [ISSN](/source/ISSN_(identifier)) [1548-9213](https://search.worldcat.org/issn/1548-9213). [PMID](/source/PMID_(identifier)) [15143204](https://pubmed.ncbi.nlm.nih.gov/15143204).

1. **[^](#cite_ref-13)** Winterbourn, Christine C. (2013-01-01), "Chapter One - The Biological Chemistry of Hydrogen Peroxide", in Cadenas, Enrique; Packer, Lester (eds.), [*Hydrogen Peroxide and Cell Signaling, Part C*](https://www.sciencedirect.com/science/article/pii/B978012405881100001X), Methods in Enzymology, vol. 528, Academic Press, pp. 3–25, [doi](/source/Doi_(identifier)):[10.1016/B978-0-12-405881-1.00001-X](https://doi.org/10.1016%2FB978-0-12-405881-1.00001-X), [ISBN](/source/ISBN_(identifier)) [978-0-12-405881-1](https://en.wikipedia.org/wiki/Special:BookSources/978-0-12-405881-1), [PMID](/source/PMID_(identifier)) [23849856](https://pubmed.ncbi.nlm.nih.gov/23849856), retrieved 2023-04-27

1. **[^](#cite_ref-14)** Brzozowska, Ewa; Bazan, Justyna; Gamian, Andrzej (2011-03-25). ["Funkcje białek bakteriofagowych"](https://doi.org/10.5604%2F17322693.936090). *Postępy Higieny i Medycyny Doświadczalnej*. **65**: 167–176. [doi](/source/Doi_(identifier)):[10.5604/17322693.936090](https://doi.org/10.5604%2F17322693.936090). [ISSN](/source/ISSN_(identifier)) [1732-2693](https://search.worldcat.org/issn/1732-2693). [PMID](/source/PMID_(identifier)) [21502693](https://pubmed.ncbi.nlm.nih.gov/21502693).

1. ^ [***a***](#cite_ref-:0_15-0) [***b***](#cite_ref-:0_15-1) Nagarajan D, Sukumaran S, Deka G, Krishnamurthy K, Atreya HS, Chandra N (June 2018). ["Design of a heme-binding peptide motif adopting a β-hairpin conformation"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005436). *The Journal of Biological Chemistry*. **293** (24): 9412–9422. [doi](/source/Doi_(identifier)):[10.1074/jbc.RA118.001768](https://doi.org/10.1074%2Fjbc.RA118.001768). [PMC](/source/PMC_(identifier)) [6005436](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005436). [PMID](/source/PMID_(identifier)) [29695501](https://pubmed.ncbi.nlm.nih.gov/29695501).

1. **[^](#cite_ref-16)** Sasaki T, Kaiser ET (1989-01-01). "Helichrome: synthesis and enzymic activity of a designed hemeprotein". *Journal of the American Chemical Society*. **111** (1): 380–381. [doi](/source/Doi_(identifier)):[10.1021/ja00183a065](https://doi.org/10.1021%2Fja00183a065). [ISSN](/source/ISSN_(identifier)) [0002-7863](https://search.worldcat.org/issn/0002-7863).

1. **[^](#cite_ref-17)** Sasaki T, Kaiser ET (January 1990). "Synthesis and structural stability of helichrome as an artificial hemeproteins". *Biopolymers*. **29** (1): 79–88. [doi](/source/Doi_(identifier)):[10.1002/bip.360290112](https://doi.org/10.1002%2Fbip.360290112). [PMID](/source/PMID_(identifier)) [2328295](https://pubmed.ncbi.nlm.nih.gov/2328295). [S2CID](/source/S2CID_(identifier)) [35536899](https://api.semanticscholar.org/CorpusID:35536899).

1. **[^](#cite_ref-18)** Isogai Y, Ota M, Fujisawa T, Izuno H, Mukai M, Nakamura H, et al. (June 1999). "Design and synthesis of a globin fold". *Biochemistry*. **38** (23): 7431–7443. [doi](/source/Doi_(identifier)):[10.1021/bi983006y](https://doi.org/10.1021%2Fbi983006y). [PMID](/source/PMID_(identifier)) [10360940](https://pubmed.ncbi.nlm.nih.gov/10360940).

1. **[^](#cite_ref-19)** Rosenblatt MM, Wang J, Suslick KS (November 2003). ["De novo designed cyclic-peptide heme complexes"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC263730). *Proceedings of the National Academy of Sciences of the United States of America*. **100** (23): 13140–13145. [Bibcode](/source/Bibcode_(identifier)):[2003PNAS..10013140R](https://ui.adsabs.harvard.edu/abs/2003PNAS..10013140R). [doi](/source/Doi_(identifier)):[10.1073/pnas.2231273100](https://doi.org/10.1073%2Fpnas.2231273100). [PMC](/source/PMC_(identifier)) [263730](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC263730). [PMID](/source/PMID_(identifier)) [14595023](https://pubmed.ncbi.nlm.nih.gov/14595023).

1. **[^](#cite_ref-20)** Robertson DE, Farid RS, Moser CC, Urbauer JL, Mulholland SE, Pidikiti R, et al. (March 1994). "Design and synthesis of multi-haem proteins". *Nature*. **368** (6470): 425–432. [Bibcode](/source/Bibcode_(identifier)):[1994Natur.368..425R](https://ui.adsabs.harvard.edu/abs/1994Natur.368..425R). [doi](/source/Doi_(identifier)):[10.1038/368425a0](https://doi.org/10.1038%2F368425a0). [PMID](/source/PMID_(identifier)) [8133888](https://pubmed.ncbi.nlm.nih.gov/8133888). [S2CID](/source/S2CID_(identifier)) [4360174](https://api.semanticscholar.org/CorpusID:4360174).

1. **[^](#cite_ref-21)** Choma CT, Lear JD, Nelson MJ, Dutton PL, Robertson DE, DeGrado WF (1994-02-01). "Design of a heme-binding four-helix bundle". *Journal of the American Chemical Society*. **116** (3): 856–865. [doi](/source/Doi_(identifier)):[10.1021/ja00082a005](https://doi.org/10.1021%2Fja00082a005). [ISSN](/source/ISSN_(identifier)) [0002-7863](https://search.worldcat.org/issn/0002-7863).

1. **[^](#cite_ref-22)** Discher BM, Noy D, Strzalka J, Ye S, Moser CC, Lear JD, et al. (September 2005). ["Design of amphiphilic protein maquettes: controlling assembly, membrane insertion, and cofactor interactions"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2574520). *Biochemistry*. **44** (37): 12329–12343. [doi](/source/Doi_(identifier)):[10.1021/bi050695m](https://doi.org/10.1021%2Fbi050695m). [PMC](/source/PMC_(identifier)) [2574520](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2574520). [PMID](/source/PMID_(identifier)) [16156646](https://pubmed.ncbi.nlm.nih.gov/16156646).

1. **[^](#cite_ref-23)** Mahajan M, Bhattacharjya S (June 2014). "Designed di-heme binding helical transmembrane protein". *ChemBioChem*. **15** (9): 1257–1262. [doi](/source/Doi_(identifier)):[10.1002/cbic.201402142](https://doi.org/10.1002%2Fcbic.201402142). [PMID](/source/PMID_(identifier)) [24829076](https://pubmed.ncbi.nlm.nih.gov/24829076). [S2CID](/source/S2CID_(identifier)) [20982919](https://api.semanticscholar.org/CorpusID:20982919).

1. **[^](#cite_ref-24)** Korendovych IV, Senes A, Kim YH, Lear JD, Fry HC, Therien MJ, et al. (November 2010). ["De novo design and molecular assembly of a transmembrane diporphyrin-binding protein complex"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3016712). *Journal of the American Chemical Society*. **132** (44): 15516–15518. [doi](/source/Doi_(identifier)):[10.1021/ja107487b](https://doi.org/10.1021%2Fja107487b). [PMC](/source/PMC_(identifier)) [3016712](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3016712). [PMID](/source/PMID_(identifier)) [20945900](https://pubmed.ncbi.nlm.nih.gov/20945900).

1. ^ [***a***](#cite_ref-:1_25-0) [***b***](#cite_ref-:1_25-1) Farid TA, Kodali G, Solomon LA, Lichtenstein BR, Sheehan MM, Fry BA, et al. (December 2013). ["Elementary tetrahelical protein design for diverse oxidoreductase functions"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034760). *Nature Chemical Biology*. **9** (12): 826–833. [doi](/source/Doi_(identifier)):[10.1038/nchembio.1362](https://doi.org/10.1038%2Fnchembio.1362). [PMC](/source/PMC_(identifier)) [4034760](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034760). [PMID](/source/PMID_(identifier)) [24121554](https://pubmed.ncbi.nlm.nih.gov/24121554).

1. **[^](#cite_ref-26)** Huang SS, Koder RL, Lewis M, Wand AJ, Dutton PL (April 2004). ["The HP-1 maquette: from an apoprotein structure to a structured hemoprotein designed to promote redox-coupled proton exchange"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC397418). *Proceedings of the National Academy of Sciences of the United States of America*. **101** (15): 5536–5541. [doi](/source/Doi_(identifier)):[10.1073/pnas.0306676101](https://doi.org/10.1073%2Fpnas.0306676101). [PMC](/source/PMC_(identifier)) [397418](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC397418). [PMID](/source/PMID_(identifier)) [15056758](https://pubmed.ncbi.nlm.nih.gov/15056758).

1. **[^](#cite_ref-27)** Faiella M, Maglio O, Nastri F, Lombardi A, Lista L, Hagen WR, Pavone V (December 2012). "De novo design, synthesis and characterisation of MP3, a new catalytic four-helix bundle hemeprotein". *Chemistry: A European Journal*. **18** (50): 15960–15971. [doi](/source/Doi_(identifier)):[10.1002/chem.201201404](https://doi.org/10.1002%2Fchem.201201404). [PMID](/source/PMID_(identifier)) [23150230](https://pubmed.ncbi.nlm.nih.gov/23150230).

1. **[^](#cite_ref-28)** Cherry JR, Lamsa MH, Schneider P, Vind J, Svendsen A, Jones A, Pedersen AH (April 1999). "Directed evolution of a fungal peroxidase". *Nature Biotechnology*. **17** (4): 379–384. [doi](/source/Doi_(identifier)):[10.1038/7939](https://doi.org/10.1038%2F7939). [PMID](/source/PMID_(identifier)) [10207888](https://pubmed.ncbi.nlm.nih.gov/10207888). [S2CID](/source/S2CID_(identifier)) [41233353](https://api.semanticscholar.org/CorpusID:41233353).

1. **[^](#cite_ref-29)** Anderson JL, Armstrong CT, Kodali G, Lichtenstein BR, Watkins DW, Mancini JA, et al. (February 2014). ["Constructing a man-made c-type cytochrome maquette *in vivo*: electron transfer, oxygen transport and conversion to a photoactive light harvesting maquette"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3952003). *Chemical Science*. **5** (2): 507–514. [doi](/source/Doi_(identifier)):[10.1039/C3SC52019F](https://doi.org/10.1039%2FC3SC52019F). [PMC](/source/PMC_(identifier)) [3952003](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3952003). [PMID](/source/PMID_(identifier)) [24634717](https://pubmed.ncbi.nlm.nih.gov/24634717).

1. **[^](#cite_ref-30)** Koder RL, Anderson JL, Solomon LA, Reddy KS, Moser CC, Dutton PL (March 2009). ["Design and engineering of an O(2) transport protein"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539743). *Nature*. **458** (7236): 305–309. [Bibcode](/source/Bibcode_(identifier)):[2009Natur.458..305K](https://ui.adsabs.harvard.edu/abs/2009Natur.458..305K). [doi](/source/Doi_(identifier)):[10.1038/nature07841](https://doi.org/10.1038%2Fnature07841). [PMC](/source/PMC_(identifier)) [3539743](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539743). [PMID](/source/PMID_(identifier)) [19295603](https://pubmed.ncbi.nlm.nih.gov/19295603).

1. **[^](#cite_ref-31)** Moffet DA, Foley J, Hecht MH (September 2003). ["Midpoint reduction potentials and heme binding stoichiometries of de novo proteins from designed combinatorial libraries"](https://doi.org/10.1016%2FS0301-4622%2803%2900072-3). *Biophysical Chemistry*. Walter Kauzmann's 85th Birthday. **105** (2–3): 231–239. [doi](/source/Doi_(identifier)):[10.1016/S0301-4622(03)00072-3](https://doi.org/10.1016%2FS0301-4622%2803%2900072-3). [PMID](/source/PMID_(identifier)) [14499895](https://pubmed.ncbi.nlm.nih.gov/14499895).

1. **[^](#cite_ref-32)** Mahajan M, Bhattacharjya S (June 2013). "β-Hairpin peptides: heme binding, catalysis, and structure in detergent micelles". *Angewandte Chemie*. **52** (25): 6430–6434. [doi](/source/Doi_(identifier)):[10.1002/anie.201300241](https://doi.org/10.1002%2Fanie.201300241). [PMID](/source/PMID_(identifier)) [23640811](https://pubmed.ncbi.nlm.nih.gov/23640811).

1. **[^](#cite_ref-33)** D'Souza A, Wu X, Yeow EK, Bhattacharjya S (May 2017). "Designed Heme-Cage β-Sheet Miniproteins". *Angewandte Chemie*. **56** (21): 5904–5908. [doi](/source/Doi_(identifier)):[10.1002/anie.201702472](https://doi.org/10.1002%2Fanie.201702472). [PMID](/source/PMID_(identifier)) [28440962](https://pubmed.ncbi.nlm.nih.gov/28440962).

1. **[^](#cite_ref-34)** D'Souza A, Mahajan M, Bhattacharjya S (April 2016). ["Designed multi-stranded heme binding β-sheet peptides in membrane"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477022). *Chemical Science*. **7** (4): 2563–2571. [doi](/source/Doi_(identifier)):[10.1039/C5SC04108B](https://doi.org/10.1039%2FC5SC04108B). [PMC](/source/PMC_(identifier)) [5477022](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477022). [PMID](/source/PMID_(identifier)) [28660027](https://pubmed.ncbi.nlm.nih.gov/28660027).

1. **[^](#cite_ref-35)** Lemon, Christopher M.; Marletta, Michael A. (2021-12-21). ["Designer Heme Proteins: Achieving Novel Function with Abiological Heme Analogues"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8754152). *Accounts of Chemical Research*. **54** (24): 4565–4575. [doi](/source/Doi_(identifier)):[10.1021/acs.accounts.1c00588](https://doi.org/10.1021%2Facs.accounts.1c00588). [ISSN](/source/ISSN_(identifier)) [0001-4842](https://search.worldcat.org/issn/0001-4842). [PMC](/source/PMC_(identifier)) [8754152](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8754152). [PMID](/source/PMID_(identifier)) [34890183](https://pubmed.ncbi.nlm.nih.gov/34890183).

## External links

- [Heme Protein Database](http://hemeprotein.info/heme.php)

- [Hemeproteins](https://meshb.nlm.nih.gov/record/ui?name=Hemeproteins) at the U.S. National Library of Medicine [Medical Subject Headings](/source/Medical_Subject_Headings) (MeSH)

v t e Proteins that contain heme (hemoproteins) Globins Hemoglobin Subunits Alpha locus on 16: α HBA1 HBA2 pseudo ζ HBZ θ HBQ1 μ HBM Beta locus on 11: β HBB δ HBD γ HBG1 HBG2 ε HBE1 Tetramers stages of development: Embryonic Hb Gower 1 (ζ2ε2) Hb Gower 2 (α2ε2) Hb Portland I (ζ2γ2) Hb Portland II (ζ2β2) Hb Portland III (ζ2δ2) Fetal HbF/Fetal (α2γ2) HbA (α2β2) Adult HbA (α2β2) HbA2 (α2δ2) HbF/Fetal (α2γ2) pathology: HbH (β4) Barts (γ4) HbD (α2βD2) HbS (α2βS2) HbC (α2βC2) HbE (α2βE2) HbO (α2βO2) Compounds Carboxyhemoglobin Carbaminohemoglobin Oxyhemoglobin/Deoxyhemoglobin Sulfhemoglobin Other human Glycated hemoglobin Methemoglobin Nonhuman Chlorocruorin Erythrocruorin Other human: Myoglobin Metmyoglobin Neuroglobin Cytoglobin plant: Leghemoglobin Other Cytochrome Cytochrome b Cytochrome P450 Methemalbumin see also disorders of globin and globulin proteins

Authority control databases International GND National United States France BnF data Israel Other Yale LUX

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Adapted from the Wikipedia article [Hemoprotein](https://en.wikipedia.org/wiki/Hemoprotein) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Hemoprotein?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.