New light on vitamin B12: The adenosylcobalamin-dependent photoreceptor protein CarH
Adenosylcobalamin (AdoCbl), or coenzyme B12, is a cofactor for enzymes important in metabolism in humans (and other mammals) and bacteria. AdoCbl contains a Co-C bond and is extremely light sensitive, but, until recently, this light sensitivity appeared to have no physiological function. Recently, A...
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| Format: | Article |
| Language: | English |
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Academy of Science of South Africa
2016-09-01
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| Series: | South African Journal of Science |
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| Online Access: | https://www.sajs.co.za/article/view/3597 |
| _version_ | 1811302886258245632 |
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| author | Susan M. Chemaly |
| author_facet | Susan M. Chemaly |
| author_sort | Susan M. Chemaly |
| collection | DOAJ |
| description | Adenosylcobalamin (AdoCbl), or coenzyme B12, is a cofactor for enzymes important in metabolism in humans (and other mammals) and bacteria. AdoCbl contains a Co-C bond and is extremely light sensitive, but, until recently, this light sensitivity appeared to have no physiological function. Recently, AdoCbl has been found to act as cofactor for a photoreceptor protein (CarH) that controls the expression of DNA coding for transcription of the proteins needed for synthesis of carotenes in certain non-photosynthetic bacteria. In 2015, the X-ray crystal structures of two dark states of the photoreceptor protein from the bacterium Thermus thermophilus were determined: CarH bound to AdoCbl and CarH bound to a large portion of the cognate DNA operator (and AdoCbl); a light state was also determined in which CarH was bound to cobalamin in which the Co-C bond had been broken. The breaking of the Co-C bond of Ado-Cbl acts as a trigger for the regulatory switch that allows the transcription of DNA. In the two dark states AdoCbl is bound to a conserved histidine from CarH, which displaces the lower 5,6-dimethylbenzimidazole ligand of AdoCbl. In the light state the 5’-deoxyadenosyl group of AdoCbl is replaced by a second histidine from CarH, giving a bis-histidine cobalamin and 4’,5’-anhydroadenosine. Genes for B12-dependent photoreceptors are widespread in bacteria. Control of DNA transcription may represent an evolutionarily ancient function of AdoCbl, possibly pre-dating its function as a protein cofactor.
Significance:
• A new function for adenosylcobalamin, a light-sensitive form of vitamin B12 with a Co-C bond, has been discovered in bacteria
• Some non-photosynthetic bacteria use adenosylcobalamin as a cofactor for the protein CarH, which controls DNA transcription
• Three X-ray crystal structures of CarH have been determined: bound to adenosylcobalamin, DNA and after light exposure
• A mechanism of action for CarH, based on its structure and on model reactions of vitamin B12, is proposed |
| first_indexed | 2024-04-13T07:37:26Z |
| format | Article |
| id | doaj.art-dd0871d190d64bdab07ca0d962c53daf |
| institution | Directory Open Access Journal |
| issn | 1996-7489 |
| language | English |
| last_indexed | 2024-04-13T07:37:26Z |
| publishDate | 2016-09-01 |
| publisher | Academy of Science of South Africa |
| record_format | Article |
| series | South African Journal of Science |
| spelling | doaj.art-dd0871d190d64bdab07ca0d962c53daf2022-12-22T02:56:06ZengAcademy of Science of South AfricaSouth African Journal of Science1996-74892016-09-011129/109910.17159/sajs.2016/201601063597New light on vitamin B12: The adenosylcobalamin-dependent photoreceptor protein CarHSusan M. Chemaly0School of Chemistry, University of the Witwatersrand, Johannesburg, South AfricaAdenosylcobalamin (AdoCbl), or coenzyme B12, is a cofactor for enzymes important in metabolism in humans (and other mammals) and bacteria. AdoCbl contains a Co-C bond and is extremely light sensitive, but, until recently, this light sensitivity appeared to have no physiological function. Recently, AdoCbl has been found to act as cofactor for a photoreceptor protein (CarH) that controls the expression of DNA coding for transcription of the proteins needed for synthesis of carotenes in certain non-photosynthetic bacteria. In 2015, the X-ray crystal structures of two dark states of the photoreceptor protein from the bacterium Thermus thermophilus were determined: CarH bound to AdoCbl and CarH bound to a large portion of the cognate DNA operator (and AdoCbl); a light state was also determined in which CarH was bound to cobalamin in which the Co-C bond had been broken. The breaking of the Co-C bond of Ado-Cbl acts as a trigger for the regulatory switch that allows the transcription of DNA. In the two dark states AdoCbl is bound to a conserved histidine from CarH, which displaces the lower 5,6-dimethylbenzimidazole ligand of AdoCbl. In the light state the 5’-deoxyadenosyl group of AdoCbl is replaced by a second histidine from CarH, giving a bis-histidine cobalamin and 4’,5’-anhydroadenosine. Genes for B12-dependent photoreceptors are widespread in bacteria. Control of DNA transcription may represent an evolutionarily ancient function of AdoCbl, possibly pre-dating its function as a protein cofactor. Significance: • A new function for adenosylcobalamin, a light-sensitive form of vitamin B12 with a Co-C bond, has been discovered in bacteria • Some non-photosynthetic bacteria use adenosylcobalamin as a cofactor for the protein CarH, which controls DNA transcription • Three X-ray crystal structures of CarH have been determined: bound to adenosylcobalamin, DNA and after light exposure • A mechanism of action for CarH, based on its structure and on model reactions of vitamin B12, is proposedhttps://www.sajs.co.za/article/view/3597photolysiscoenzyme B12light-sensing proteinDNA transcriptionX-ray crystallography |
| spellingShingle | Susan M. Chemaly New light on vitamin B12: The adenosylcobalamin-dependent photoreceptor protein CarH South African Journal of Science photolysis coenzyme B12 light-sensing protein DNA transcription X-ray crystallography |
| title | New light on vitamin B12: The adenosylcobalamin-dependent photoreceptor protein CarH |
| title_full | New light on vitamin B12: The adenosylcobalamin-dependent photoreceptor protein CarH |
| title_fullStr | New light on vitamin B12: The adenosylcobalamin-dependent photoreceptor protein CarH |
| title_full_unstemmed | New light on vitamin B12: The adenosylcobalamin-dependent photoreceptor protein CarH |
| title_short | New light on vitamin B12: The adenosylcobalamin-dependent photoreceptor protein CarH |
| title_sort | new light on vitamin b12 the adenosylcobalamin dependent photoreceptor protein carh |
| topic | photolysis coenzyme B12 light-sensing protein DNA transcription X-ray crystallography |
| url | https://www.sajs.co.za/article/view/3597 |
| work_keys_str_mv | AT susanmchemaly newlightonvitaminb12theadenosylcobalamindependentphotoreceptorproteincarh |