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Abstract
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
 
 
Highlights
It is appropriate that in 2015, the UNESCO year of light, the X-ray crystal structure of a novel coenzyme B12dependent photoreceptor protein was reported.[1]
Vitamin B12 was first discovered as cyanocobalamin (CNCbl), an inactive form of the vitamin, as an artefact of the isolation procedure, which utilised cyanide. (For reviews on vitamin B12, see 2–5)
Bacteria utilise MeCbl in the fixation of carbon dioxide through the acetyl-coenzyme A (CoA) pathway, methanogenesis and in a variety of methylation reactions, including some involved in the synthesis of the corrinoid precursors of cobalamins
Summary
It is appropriate that in 2015, the UNESCO year of light, the X-ray crystal structure of a novel coenzyme B12dependent photoreceptor protein was reported.[1]. The mechanism of action of AdoCbl-requiring enzymes involves homolysis of the Co-C bond of AdoCbl to give cobalamin in the Co(II) oxidation state and the 5’-deoxyadenosyl free radical. This reaction is similar to that taking place when free AdoCbl is photolysed. In the free dark state, CarH is a tetramer with one molecule of AdoCbl bound to each monomer.[1] Each monomer has one domain that attaches to DNA at the N-terminal end and a second domain that binds the light-sensing AdoCbl molecule at the C-terminal end. A histidine, His[132], on the helical bundle has shifted into a suitable position to coordinate with Co(III) on the cobalamin through its imidazole side-chain
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