Abstract

CHEMALY, Susan M.. New light on vitamin B₁₂: The adenosylcobalamin-dependent photoreceptor protein CarH. S. Afr. j. sci. [online]. 2016, vol.112, n.9-10, pp.1-9. ISSN 1996-7489.  http://dx.doi.org/10.17159/sajs.2016/20160106.

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

Keywords : photolysis; coenzyme B₁₂; light-sensing protein; DNA transcription; X-ray crystallography.

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