Tryptophan tryptophylquinone (TTQ) formation
Tryptophan tryptophylquinone (TTQ) is an enzyme cofactor, generated by posttranslational modification of amino acids within the protein. Methylamine dehydrogenase (MADH), an amine dehydrogenase, requires TTQ for its catalytic function.
- Davidson, V. L.; Liu, A. (2012). “Tryptophan tryptophylquinone biosynthesis: A radical approach to posttranslational modification, by Victor L. Davidson1 and Aimin Liu2, on National Center for Biotechnology Information, U.S. National Library of Medicine, published 2012 Jan 28. doi: 10.1016/j.bbapap.2012.01.008”. Biochimica et Biophysica Acta. 1824 (11): 1299–1305. doi:10.1016/j.bbapap.2012.01.008. PMC 3432176. PMID 22314272. Davidson VL, Liu A (2009). “Uncovering novel biochemistry in the mechanism of tryptophan tryptophylquinone cofactor biosynthesis”. Curr. Opin. Chem. Biol. 13 (4): 469–474. doi:10.1016/j.cbpa.2009.06.026. PMC 2749888. PMID 19648051.
From Wikipedia where this page was last updated June 22, 2022
See also
Amicyanin is a type I copper protein that plays an integral role in electron transfer. In bacteria such as Paracoccus denitrificans, amicyanin is part of a three-member redox complex, along with methylamine dehydrogenase (MADH) and cytochrome c-551i.
Paracoccus denitrificans, is a coccoid bacterium known for its nitrate reducing properties, its ability to replicate under conditions of hypergravity and for being a relative of the eukaryotic mitochondrion (endosymbiotic theory).Formerly known as Micrococcus denitrificans, it was first isolated in 1910 by Martinus Beijerinck, a Dutch microbiologist.[Beijerinck, M. W.; Minkman, D. C. J. (1910). “Bildung und Verbrauch von Stickoxydul durch Bakterien”. Zentralblatt für Bakteriologie, Parasitenkunde, Infektionskrankheiten und Hygiene, Abteilung II. 25: 30–63.] The bacterium was reclassified in 1969 to Paracoccus denitrificans by D.H. Davis.[Davis, D. H.; et al. (1969). “Proposal to reject the genus Hydrogenomonas: taxonomic implications”. Int J Syst Bacteriol. 19 (4): 375–390. doi:10.1099/00207713-19-4-375.] The genome of P. denitrificans was sequenced in 2004.[Archived original web report of genome sequencing of Paracoccus denitrificans by Oak Ridge National Laboratory’s human genome sequencing project of 08 Jun 2004 and 11 Sep 2006. Entry for P. denitrificans in Kyoto Encyclopedia of Genes and Genomes.]
Amine Dehydrogenase (EC 1.4.99.3), also known as methylamine dehydrogenase (MADH), is a tryptophan tryptophylquinone-dependent (TTQ-dependent) enzyme that catalyzes the oxidative deamination of a primary amine to an aldehyde and ammonia. The reaction occurs as follows:
RCH2NH2 + H2O + acceptor → RCHO + NH3 + reduced acceptor
Amine dehydrogenase possesses an α2β2 structure with each smaller β subunit possessing a TTQ protein cofactor. Amine dehydrogenase, studied in Paracoccus denitrificans, at least transiently forms a ternary complex to catalyze methylamine-dependent cytochrome c-551i reduction. Within this complex, electrons are transferred from the TTQ cofactor of MADH to the Type 1 copper center of amicyanin, and then to the heme of the cytochrome. [Davidson VL (August 2004). “Electron transfer in quinoproteins”. Archives of Biochemistry and Biophysics. 428 (1): 32–40. doi:10.1016/j.abb.2004.03.022. PMID 15234267.]
Heme or haem is a precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver.[Bloomer, Joseph R. (1998). “Liver metabolism of porphyrins and haem”. Journal of Gastroenterology and Hepatology. 13 (3): 324–329. doi:10.1111/j.1440-1746.1998.01548.x. PMID 9570250. S2CID 25224821.] In biochemical terms, heme is a coordination complex “consisting of an iron ion coordinated to a porphyrin acting as a tetradentate ligand, and to one or two axial ligands.”[Chemistry, International Union of Pure and Applied (2009). “Hemes (heme derivatives)”. IUPAC Compendium of Chemical Terminology. iupac.org. IUPAC. doi:10.1351/goldbook.H02773. ISBN 978-0-9678550-9-7. Archived from the original on 22 August 2017. Retrieved 28 April 2018.] The definition is loose, and many depictions omit the axial ligands.[A standard biochemistry text defines heme as the “iron-porphyrin prosthetic group of heme proteins”(Nelson, D. L.; Cox, M. M. “Lehninger, Principles of Biochemistry” 3rd Ed. Worth Publishing: New York, 2000. ISBN 1-57259-153-6.)] Among the metalloporphyrins deployed by metalloproteins as prosthetic groups, heme is one of the most widely used[Poulos, Thomas L. (2014-04-09). “Heme Enzyme Structure and Function”. Chemical Reviews. 114 (7): 3919–3962. doi:10.1021/cr400415k. ISSN 0009-2665. PMC 3981943. PMID 24400737. ^] and defines a family of proteins known as hemoproteins. Hemes are most commonly recognized as components of hemoglobin, the red pigment in blood, but are also found in a number of other biologically important hemoproteins such as myoglobin, cytochromes, catalases, heme peroxidase, and endothelial nitric oxide synthase.[Paoli, M. (2002). “Structure-function relationships in heme-proteins” (PDF). DNA Cell Biol. 21 (4): 271–280. doi:10.1089/104454902753759690. hdl:20.500.11820/67200894-eb9f-47a2-9542-02877d41fdd7. PMID 12042067. S2CID 12806393. Archived (PDF) from the original on 2018-07-24.][Alderton, W.K. (2001). “Nitric oxide synthases: structure, function and inhibition”. Biochem. J. 357 (3): 593–615. doi:10.1042/bj3570593. PMC 1221991. PMID 11463332.] The word haem is derived from Greek αἷμα haima meaning “blood”.
Cytochromes are redox-active proteins containing a heme, with a central iron (Fe) atom at its core, as a cofactor. They are involved in electron transport chain and redox catalysis. They are classified according to the type of heme and its mode of binding. Four varieties are recognized by the International Union of Biochemistry and Molecular Biology (IUBMB), cytochromes a, cytochromes b, cytochromes c and cytochrome d.[“Nomenclature Committee of the International Union of Biochemistry (NC-IUB). Nomenclature of electron-transfer proteins. Recommendations 1989”. Journal of Biological Chemistry. 267 (1): 665–677. 1992-01-05. doi:10.1016/S0021-9258(18)48544-4. ISSN 0021-9258. PMID 1309757.] Cytochrome function is linked to the reversible redox change from ferrous (Fe(II)) to the ferric (Fe(III)) oxidation state of the iron found in the heme core.[ L., Lehninger, Albert (2000). Lehninger Principles of Biochemistry (3rd ed.). New York: Worth Publishers. ISBN 978-1572591530. OCLC 42619569.] In addition to the classification by the IUBMB into four cytochrome classes, several additional classifications such as cytochrome o[Puustinen, A.; Wikström, M. (1991-07-15). “The heme groups of cytochrome o from Escherichia coli”. Proceedings of the National Academy of Sciences. 88 (14): 6122–6126. Bibcode:1991PNAS…88.6122P. doi:10.1073/pnas.88.14.6122. ISSN 0027-8424. PMC 52034. PMID 2068092.] and cytochrome P450 can be found in biochemical literature. Cytochromes were initially described in 1884 by Charles Alexander MacMunn as respiratory pigments (myohematin or histohematin).[Mac Munn, C. A. (1886). “Researches on Myohaematin and the Histohaematins”. Philosophical Transactions of the Royal Society of London. 177: 267–298. doi:10.1098/rstl.1886.0007. JSTOR 109482. S2CID 110335335.] In the 1920s, Keilin rediscovered these respiratory pigments and named them the cytochromes, or “cellular pigments”.[Keilin, D. (1925-08-01). “On cytochrome, a respiratory pigment, common to animals, yeast, and higher plants”. Proc. R. Soc. Lond. B. 98 (690): 312–339. Bibcode:1925RSPSB..98..312K. doi:10.1098/rspb.1925.0039. ISSN 0950-1193.]Keilen is most known for his research and rediscovery of cytochrome[Ferguson, S. J. (2001). “Keilin’s Cytochromes: How Bacteria Use Them, Vary Them and Make Them”. Biochemical Society Transactions. 29 (6): 629–640. doi:10.1042/bst0290629.] C. A. MacMunn”s discovery had been forgotten or misunderstood.[Hartree, E. F. (1 October 1973). “The discovery of cytochrome”. Biochemical Education. 1 (4): 69–71. doi:10.1016/0307-4412(73)90074-5.]He classified these heme proteins on the basis of the position of their lowest energy absorption band in their reduced state, as cytochromes a (605 nm), b (≈565 nm), and c (550 nm). The ultra-violet (UV) to visible spectroscopic signatures of hemes are still used to identify heme type from the reduced bis-pyridine-ligated state, i.e., the pyridine hemochrome method. Within each class, cytochrome a, b, or c, early cytochromes are numbered consecutively, e.g. cyt c, cyt c1, and cyt c2, with more recent examples designated by their reduced state R-band maximum, e.g. cyt c559.[Reedy, C. J.; Gibney, B. R. (February 2004). “Heme protein assemblies”. Chem Rev. 104 (2): 617–49. doi:10.1021/cr0206115. PMID 14871137] The heme group is a highly conjugated ring system (which allows its electrons to be very mobile) surrounding an iron ion. The iron in cytochromes usually exists in a ferrous (Fe2+) and a ferric (Fe3+) state with a ferroxo (Fe4+) state found in catalytic intermediates.[ “Nomenclature Committee of the International Union of Biochemistry (NC-IUB). Nomenclature of electron-transfer proteins. Recommendations 1989”. Journal of Biological Chemistry. 267 (1): 665–677. 1992-01-05. doi:10.1016/S0021-9258(18)48544-4. ISSN 0021-9258. PMID 1309757.] Cytochromes are, thus, capable of performing electron transfer reactions and catalysis by reduction or oxidation of their heme iron. The cellular location of cytochromes depends on their function. They can be found as globular proteins and membrane proteins. In the process of oxidative phosphorylation, a globular cytochrome cc protein is involved in the electron transfer from the membrane-bound complex III to complex IV. Complex III itself is composed of several subunits, one of which is a b-type cytochrome while another one is a c-type cytochrome. Both domains are involved in electron transfer within the complex. Complex IV contains a cytochrome a/a3-domain that transfers electrons and catalyzes the reaction of oxygen to water. Photosystem II, the first protein complex in the light-dependent reactions of oxygenic photosynthesis, contains a cytochrome b subunit. Cyclooxygenase 2, an enzyme involved in inflammation, is a cytochrome b protein. In the early 1960s, a linear evolution of cytochromes was suggested by Emanuel Margoliash[Margoliash, E. (1963). “Primary Structure and Evolution of Cytochrome C”. Proceedings of the National Academy of Sciences of the United States of America. 50 (4): 672–679. Bibcode:1963PNAS…50..672M. doi:10.1073/pnas.50.4.672. ISSN 0027-8424. PMC 221244. PMID 14077496.] that led to the molecular clock hypothesis. The apparently constant evolution rate of cytochromes can be a helpful tool in trying to determine when various organisms may have diverged from a common ancestor.[Kumar, Sudhir (2005). “Molecular clocks: four decades of evolution”. Nature Reviews. Genetics. 6 (8): 654–662. doi:10.1038/nrg1659. ISSN 1471-0056. PMID 16136655. S2CID 14261833.] Several kinds of cytochrome exist and can be distinguished by spectroscopy, exact structure of the heme group, inhibitor sensitivity, and reduction potential.[ “Investigation of biological oxidation, oxidative phosphorylation and ATP synthesis. Inhibitor and Uncouplers of oxidative phosphorylation”. Retrieved 2020-02-02.] Four types of cytochromes are distinguished by their prosthetic groups:
| Type | Prosthetic group |
|---|---|
| Cytochrome a | heme A |
| Cytochrome b | heme B |
| Cytochrome c | heme C (covalently bound heme b)[Cytochrome+c+Group at the U.S. National Library of Medicine Medical Subject Headings (MeSH).] |
| Cytochrome d | heme D (Heme B with γ-spirolactone)[Murshudov, G.; Grebenko, A.; Barynin, V.; Dauter, Z.; Wilson, K.; Vainshtein, B.; Melik-Adamyan, W.; Bravo, J.; Ferrán, J.; Ferrer, J. C.; Switala, J.; Loewen, P. C.; Fita, I. (1996). “Structure of the heme d of Penicillium vitale and Escherichia coli catalases”. The Journal of Biological Chemistry. 271 (15): 8863–8868. doi:10.1074/jbc.271.15.8863. PMID 8621527.] |
There is no “cytochrome e,” but cytochrome f, found in the cytochrome b6f complex of plants is a c-type cytochrome.[Bendall, Derek S. (2004). “The Unfinished Story of Cytochrome f”. Photosynthesis Research. 80 (1–3): 265–276. doi:10.1023/b:pres.0000030454.23940.f9. ISSN 0166-8595. PMID 16328825. S2CID 16716904.] In mitochondria and chloroplasts, these cytochromes are often combined in electron transport and related metabolic pathways:[Doidge, Norman (2015). The brain’s way of healing : remarkable discoveries and recoveries from the frontiers of neuroplasticity. Penguin Group. p. 173. ISBN 978-0-698-19143-3.]
| Cytochromes | Combination |
|---|---|
| a and a3 | Cytochrome c oxidase (“Complex IV”) with electrons delivered to complex by soluble cytochrome c (hence the name) |
| b and c1 | Coenzyme Q – cytochrome c reductase (“Complex III”) |
| b6 and f | Plastoquinol—plastocyanin reductase |
A distinct family of cytochromes is the cytochrome P450 family, so named for the characteristic Soret peak formed by absorbance of light at wavelengths near 450 nm when the heme iron is reduced (with sodium dithionite) and complexed to carbon monoxide. These enzymes are primarily involved in steroidogenesis and detoxification.[ Miller, Walter L.; Gucev, Zoran S. (2014), “Disorders in the Initial Steps in Steroidogenesis”, Genetic Steroid Disorders, Elsevier, pp. 145–164, doi:10.1016/b978-0-12-416006-4.00011-9, ISBN 9780124160064][ “Investigation of biological oxidation, oxidative phosphorylation and ATP synthesis. Inhibitor and Uncouplers of oxidative phosphorylation”. Retrieved 2020-02-02.]
In the electron transfer mechanism from MADH to heme, amicyanin acts as an electron-accepting intermediate. In this reaction, MADH catalyzes the oxidative deamination of methylamine to formaldehyde plus ammonia. The tryptophan tryptophylquinone (TTQ) group of MADH then donates electrons to the copper centre of amicyanin, which in turn gives the electrons to the heme of the cytochrome c. In P. denitrificans, amicyanin is absolutely required for electron transfer from MADH to c-type cytochromes. It has been shown that inactivation of amicyanin by gene replacement in vivo results in complete loss of ability to grow on methylamine. As a type I copper protein, amicyanin contains one copper atom coordinated by two histidine residues and a cysteine residue in a trigonal planar structure along with an axial methionine residue ligand. Alterations from this particular coordination of the copper centre are found to negatively alter the redox potential of amicyanin. In P. denitrificans, amicyanin exists in a three-part complex along with MADH and cytochrome c-551i. This is the only redox complex composed of three weakly associated proteins naturally observed.
References
1. Victor L. Davidson and Limei Hsu Jones, Biochemistry 1996, 35, 8120-8125.
2. Arnout P. Kalverda, Jesus Salgado, Christopher Dennison, and Gerard W. Canters, Biochemistry 1996, 35, 3085-3092.
3. Victor L. Davidson and Dapeng Sun, J. Am. Chem. Soc. 2003, 125, 3224-3225.
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