Cobamides are a class of compounds that function as cofactors in various enzymatic reactions, containing a corrin ring similar to vitamin B12, but with different substituents on the benzimidazole moiety, and can be found in certain bacteria and archaea.
A family of gram-negative bacteria, in the phylum FIRMICUTES.
Compounds with a BENZENE fused to IMIDAZOLES.
A cobalt-containing coordination compound produced by intestinal micro-organisms and found also in soil and water. Higher plants do not concentrate vitamin B 12 from the soil and so are a poor source of the substance as compared with animal tissues. INTRINSIC FACTOR is important for the assimilation of vitamin B 12.

Binding of Cob(II)alamin to the adenosylcobalamin-dependent ribonucleotide reductase from Lactobacillus leichmannii. Identification of dimethylbenzimidazole as the axial ligand. (1/283)

The ribonucleoside triphosphate reductase (RTPR) from Lactobacillus leichmannii catalyzes the reduction of nucleoside 5'-triphosphates to 2'-deoxynucleoside 5'-triphosphates and uses coenzyme B12, adenosylcobalamin (AdoCbl), as a cofactor. Use of a mechanism-based inhibitor, 2'-deoxy-2'-methylenecytidine 5'-triphosphate, and isotopically labeled RTPR and AdoCbl in conjunction with EPR spectroscopy has allowed identification of the lower axial ligand of cob(II)alamin when bound to RTPR. In common with the AdoCbl-dependent enzymes catalyzing irreversible heteroatom migrations and in contrast to the enzymes catalyzing reversible carbon skeleton rearrangements, the dimethylbenzimidazole moiety of the cofactor is not displaced by a protein histidine upon binding to RTPR.  (+info)

The reaction of the substrate analog 2-ketoglutarate with adenosylcobalamin-dependent glutamate mutase. (2/283)

Glutamate mutase is one of several adenosylcobalamin-dependent enzymes that catalyze unusual rearrangements that proceed through a mechanism involving free radical intermediates. The enzyme exhibits remarkable specificity, and so far no molecules other than L-glutamate and L-threo-3-methylaspartate have been found to be substrates. Here we describe the reaction of glutamate mutase with the substrate analog, 2-ketoglutarate. Binding of 2-ketoglutarate (or its hydrate) to the holoenzyme elicits a change in the UV-visible spectrum consistent with the formation of cob(II)alamin on the enzyme. 2-ketoglutarate undergoes rapid exchange of tritium between the 5'-position of the coenzyme and C-4 of 2-ketoglutarate, consistent with the formation of a 2-ketoglutaryl radical analogous to that formed with glutamate. Under aerobic conditions this leads to the slow inactivation of the enzyme, presumably through reaction of free radical species with oxygen. Despite the formation of a substrate-like radical, no rearrangement of 2-ketoglutarate to 3-methyloxalacetate could be detected. The results indicate that formation of the C-4 radical of 2-ketoglutarate is a facile process but that it does not undergo further reactions, suggesting that this may be a useful substrate analog with which to investigate the mechanism of coenzyme homolysis.  (+info)

Methanol:coenzyme M methyltransferase from Methanosarcina barkeri -- substitution of the corrinoid harbouring subunit MtaC by free cob(I)alamin. (3/283)

Methyl-coenzyme M formation from coenzyme M and methanol in Methanosarcina barkeri is catalysed by an enzyme system composed of three polypeptides MtaA, MtaB and MtaC, the latter of which harbours a corrinoid prosthetic group. We report here that MtaC can be substituted by free cob(I)alamin which is methylated with methanol in an MtaB-catalysed reaction and demethylated with coenzyme M in an MtaA-catalysed reaction. Methyl transfer from methanol to coenzyme M was found to proceed at a relatively high specific activity at micromolar concentrations of cob(I)alamin. This finding was surprising because the methylation of cob(I)alamin catalysed by MtaB alone and the demethylation of methylcob(III)alamin catalysed by MtaA alone exhibit apparent Km for cob(I)alamin and methylcob(III)alamin of above 1 mm. A possible explanation is that MtaA positively affects the MtaB catalytic efficiency and vice versa by decreasing the apparent Km for their corrinoid substrates. Activation of MtaA by MtaB was methanol-dependent. In the assay for methanol:coenzyme M methyltransferase activity cob(I)alamin could be substituted by cob(I)inamide which is devoid of the nucleotide loop. Substitution was, however, only possible when the assays were supplemented with imidazole: approximately 1 mm imidazole being required for half-maximal activity. Methylation of cob(I)inamide with methanol was found to be dependent on imidazole but not on the demethylation of methylcob(III)inamide with coenzyme M. The demethylation reaction was even inhibited by imidazole. The structure and catalytic mechanism of the MtaABC complex are compared with the cobalamin-dependent methionine synthase.  (+info)

Adenosylcobalamin-mediated methyl transfer by toluate cis-dihydrodiol dehydrogenase of the TOL plasmid pWW0. (4/283)

We identified and characterized a methyl transfer activity of the toluate cis-dihydrodiol (4-methyl-3,5-cyclohexadiene-cis-1, 2-diol-1-carboxylic acid) dehydrogenase of the TOL plasmid pWW0 towards toluene cis-dihydrodiol (3-methyl-4,5-cyclohexadiene-cis-1, 2-diol). When the purified enzyme from the recombinant Escherichia coli containing the xylL gene was incubated with toluene cis-dihydrodiol in the presence of NAD+, the end products differed depending on the presence of adenosylcobalamin (coenzyme B12). The enzyme yielded catechol in the presence of adenosylcobalamin, while it gave 3-methylcatechol in the absence of the cofactor. Adenosylcobalamin was transformed to methylcobalamin as a result of the enzyme reaction, which indicates that the methyl group of the substrate was transferred to adenosylcobalamin. Other derivatives of the cobalamin such as aquo (hydroxy)- and cyanocobalamin did not mediate the methyl transfer reaction. The dehydrogenation and methyl transfer reactions were assumed to occur concomitantly, and the methyl transfer reaction seemed to depend on the dehydrogenation. To our knowledge, the enzyme is the first dehydrogenase that shows a methyl transfer activity as well.  (+info)

Co-ordinate variations in methylmalonyl-CoA mutase and methionine synthase, and the cobalamin cofactors in human glioma cells during nitrous oxide exposure and the subsequent recovery phase. (5/283)

We investigated the co-ordinate variations of the two cobalamin (Cbl)-dependent enzymes, methionine synthase (MS) and methylmalonyl-CoA mutase (MCM), and measured the levels of their respective cofactors, methylcobalamin (CH3Cbl) and adenosylcobalamin (AdoCbl) in cultured human glioma cells during nitrous oxide exposure and during a subsequent recovery period of culture in a nitrous oxide-free atmosphere (air). In agreement with published data, MS as the primary target of nitrous oxide was inactivated rapidly (initial rate of 0.06 h(-1)), followed by reduction of CH3Cbl (to <20%). Both enzyme activity and cofactor levels recovered rapidly when the cells were subsequently cultured in air, but the recovery was completely blocked by the protein-synthesis inhibitor, cycloheximide. During MS inactivation, there was a reduction of cellular AdoCbl and holo-MCM activity (measured in the absence of exogenous AdoCbl) to about 50% of pre-treatment levels. When the cells were transferred to air, both AdoCbl and holo-MCM activity recovered, albeit more slowly than the MS system. Notably, the regain of the holo-MCM and AdoCbl was enhanced rather than inhibited by cycloheximide. These findings confirm irreversible damage of MS by nitrous oxide; hence, synthesis of the enzyme is required to restore its activity. In contrast, restoration of holo-MCM activity is only dependent on repletion of the AdoCbl cofactor. We also observed a synchronous fluctuation in AdoCbl and the much larger hydroxycobalamin pool during the inactivation and recovery phase, suggesting that the loss and repletion of AdoCbl reflect changes in intracellular Cbl homoeostasis. Our data demonstrate that the nitrous oxide-induced changes in MS and CH3Cbl are associated with reversible changes in both MCM holoactivity and the AdoCbl level, suggesting co-ordinate distribution of Cbl cofactors during depletion and repletion.  (+info)

Identification and expression of the genes encoding a reactivating factor for adenosylcobalamin-dependent glycerol dehydratase. (6/283)

Adenosylcobalamin-dependent glycerol dehydratase undergoes inactivation by glycerol, the physiological substrate, during catalysis. In permeabilized cells of Klebsiella pneumoniae, the inactivated enzyme is reactivated in the presence of ATP, Mg2+, and adenosylcobalamin. We identified the two open reading frames as the genes for a reactivating factor for glycerol dehydratase and designated them gdrA and gdrB. The reactivation of the inactivated glycerol dehydratase by the gene products was confirmed in permeabilized recombinant Escherichia coli cells coexpressing GdrA and GdrB proteins with glycerol dehydratase.  (+info)

Structure and dynamics of the B12-binding subunit of glutamate mutase from Clostridium cochlearium. (7/283)

Glutamate mutase (Glm) is an adenosylcobamide-dependent enzyme that catalyzes the reversible rearrangement of (2S)-glutamate to (2S, 3S)-3-methylaspartate. The active enzyme from Clostridium cochlearium consists of two subunits (of 53.6 and 14.8 kDa) as an alpha2beta2 tetramer, whose assembly is mediated by coenzyme B12. The smaller of the protein components, GlmS, has been suggested to be the B12-binding subunit. Here we report the solution structure of GlmS, determined from a heteronuclear NMR-study, and the analysis of important dynamical aspects of this apoenzyme subunit. The global fold and dynamic behavior of GlmS in solution are similar to those of the corresponding subunit MutS from C. tetanomorphum, which has previously been investigated using NMR-spectroscopy. Both solution structures of the two Glm B12-binding subunits share striking similarities with that determined by crystallography for the B12-binding domain of methylmalonyl CoA mutase (Mcm) from Propionibacterium shermanii, which is B12 bound. In the crystal structure a conserved histidine residue was found to be coordinated to cobalt, displacing the endogenous axial ligand of the cobamide. However, in GlmS and MutS the sequence motif, Asp-x-His-x-x-Gly, which includes the cobalt-coordinating histidine residue, and a predicted alpha-helical region following the motif, are present as an unstructured and highly mobile loop. In the absence of coenzyme, the B12-binding site apparently is only partially formed. By comparing the crystal structure of Mcm with the solution structures of B12-free GlmS and MutS, a consistent picture on the mechanism of B12 binding has been obtained. Important elements of the binding site only become structured upon binding B12; these include the cobalt-coordinating histidine residue, and an alpha helix that forms one side of the cleft accommodating the nucleotide 'tail' of the coenzyme.  (+info)

Isolation of acetate auxotrophs of the methane-producing archaeon Methanococcus maripaludis by random insertional mutagenesis. (8/283)

To learn more about autotrophic growth of methanococci, we isolated nine conditional mutants of Methanococcus maripaludis after transformation of the wild type with a random library in pMEB.2, a suicide plasmid bearing the puromycin-resistance cassette pac. These mutants grew poorly in mineral medium and required acetate or complex organic supplements such as yeast extract for normal growth. One mutant, JJ104, was a leaky acetate auxotroph. A plasmid, pWDK104, was recovered from this mutant by electroporation of a plasmid preparation into Escherichia coli. Transformation of wild-type M. maripaludis with pWDK104 produced JJ104-1, a mutant with the same phenotype as JJ104, thus establishing that insertion of pWDK104 into the genome was responsible for the phenotype. pWDK104 contained portions of the methanococcal genes encoding an ABC transporter closely related to MJ1367-MJ1368 of M. jannaschii. Because high levels of molybdate, tungstate, and selenite restored growth to wild-type levels, this transporter may be specific for these oxyanions. A second acetate auxotroph, JJ117, had an absolute growth requirement for either acetate or cobalamin, and wild-type growth was observed only in the presence of both. Cobinamide, 5', 6'-dimethylbenzimidazole, and 2-aminopropanol did not replace cobalamin. This phenotype was correlated with tandem insertions in the genome but not single insertions and appeared to have resulted from an indirect effect on cobamide metabolism. Plasmids rescued from other mutants contained portions of ORFs denoted in M. jannaschii as endoglucanase (MJ0555), transketolase (MJ0681), thiamine biosynthetic protein thiI (MJ0931), and several hypothetical proteins (MJ1031, MJ0835, and MJ0835.1).  (+info)

Cobamides are a class of compounds that are structurally related to vitamin B12 (cobalamin). They consist of a corrin ring, which is a large heterocyclic ring made up of four pyrrole rings, and a cobalt ion in the center. The lower axial ligand of the cobalt ion can be a variety of different groups, including cyano, hydroxo, methyl, or 5'-deoxyadenosyl groups.

Cobamides are involved in a number of important biological processes, including the synthesis of amino acids and nucleotides, the metabolism of fatty acids and cholesterol, and the regulation of gene expression. They function as cofactors for enzymes called cobamide-dependent methyltransferases, which transfer methyl groups (CH3) from one molecule to another.

Cobamides are found in a wide variety of organisms, including bacteria, archaea, and eukaryotes. In humans, the most important cobamide is vitamin B12, which is essential for the normal functioning of the nervous system and the production of red blood cells. Vitamin B12 deficiency can lead to neurological problems and anemia.

Veillonellaceae is a family of Gram-negative, anaerobic bacteria found in various environments, including the human mouth and gut. The bacteria are known for their ability to produce acetic and lactic acid as end products of their metabolism. They are often part of the normal microbiota of the body, but they can also be associated with certain infections, particularly in individuals with weakened immune systems.

It's important to note that while Veillonellaceae bacteria are generally considered to be commensal organisms, meaning they exist harmoniously with their human hosts, they have been implicated in some disease states, such as periodontitis (gum disease) and bacterial pneumonia. However, more research is needed to fully understand the role of these bacteria in health and disease.

Benzimidazoles are a class of heterocyclic compounds containing a benzene fused to a imidazole ring. They have a wide range of pharmacological activities and are used in the treatment of various diseases. Some of the benzimidazoles are used as antiparasitics, such as albendazole and mebendazole, which are effective against a variety of worm infestations. Other benzimidazoles have antifungal properties, such as thiabendazole and fuberidazole, and are used to treat fungal infections. Additionally, some benzimidazoles have been found to have anti-cancer properties and are being investigated for their potential use in cancer therapy.

Vitamin B12, also known as cobalamin, is a water-soluble vitamin that plays a crucial role in the synthesis of DNA, formation of red blood cells, and maintenance of the nervous system. It is involved in the metabolism of every cell in the body, particularly affecting DNA regulation and neurological function.

Vitamin B12 is unique among vitamins because it contains a metal ion, cobalt, from which its name is derived. This vitamin can be synthesized only by certain types of bacteria and is not produced by plants or animals. The major sources of vitamin B12 in the human diet include animal-derived foods such as meat, fish, poultry, eggs, and dairy products, as well as fortified plant-based milk alternatives and breakfast cereals.

Deficiency in vitamin B12 can lead to various health issues, including megaloblastic anemia, fatigue, neurological symptoms such as numbness and tingling in the extremities, memory loss, and depression. Since vitamin B12 is not readily available from plant-based sources, vegetarians and vegans are at a higher risk of deficiency and may require supplementation or fortified foods to meet their daily requirements.

Perlman D (1959). "Microbial synthesis of cobamides". Advances in Applied Microbiology. 1: 87-122. doi:10.1016/S0065-2164(08) ...
Perlman D (1959). "Microbial synthesis of cobamides". Advances in Applied Microbiology. 1: 87-122. doi:10.1016/S0065-2164(08) ...
Blakley RL (May 1965). "Cobamides and ribonucleotide reduction. I. Cobamide stimulation of ribonucleotide reduction in extracts ...
Sokolovskaya, Olga M.; Shelton, Amanda N.; Taga, Michiko E. (2020). "Sharing vitamins: Cobamides unveil microbial interactions ...
"Structural investigation of the biosynthesis of alternative lower ligands for cobamides by nicotinate mononucleotide: 5,6- ...
... cobamides MeSH D03.383.129.578.840.437.777.560 - hydroxocobalamin MeSH D03.383.129.578.840.500 - porphyrins MeSH D03.383. ... cobamides MeSH D03.549.909.437.777.560 - hydroxocobalamin MeSH D03.549.909.500 - porphyrins MeSH D03.549.909.500.250 - ...
... cobamides MeSH D04.345.783.437.777.560 - hydroxocobalamin MeSH D04.345.783.500 - porphyrins MeSH D04.345.783.500.250 - ...
... and other cobamides. Previously, mutational analysis identified a class of alleles (class M) that failed to restore AdoCbl ... and other cobamides. Previously, mutational analysis identified a class of alleles (class M) that failed to restore AdoCbl ...
Perlman D (1959). "Microbial synthesis of cobamides". Advances in Applied Microbiology. 1: 87-122. doi:10.1016/S0065-2164(08) ...
Nearly all seaweed tested has been revealed to contain vitamin B12 analogs (that is, chemically similar) called cobamides that ...
Cobamides Entry term(s). B12 Coenzymes, Vitamin Coenzymes, Vitamin B12 Deoxyadenosinecobalamins Vitamin B 12 Coenzymes Vitamin ... deficiency: coordinate COBAMIDES /defic (IM) with VITAMIN B 12 DEFICIENCY (IM). Allowable Qualifiers:. AA analogs & derivatives ... Cobamides Entry term(s):. B12 Coenzymes, Vitamin. Coenzymes, Vitamin B12. Deoxyadenosinecobalamins. Vitamin B 12 Coenzymes. ... Cobamides - Preferred Concept UI. M0004665. Preferred term. ...
Cobamides are a family of enzyme cofactors that are required by organisms in all domains of life. Over a dozen cobamides exist ... Cobamides have structural variability in the lower ligand, and selectivity for particular cobamides has been observed in most ... Cobamides are exclusively produced by a subset of prokaryotes. Importantly, the bacteria and archaea that synthesize cobamides ... and produces other cobamides if provided an alternative lower ligand. The ability of C. difficile 630 Δerm to take up cobamides ...
Cobamides D3.549.909.437.777.270 D3.633.400.909.437.777.270 Cocaine D4.75.80.875.99.722.388 D3.605.84.500.722.388 Cochlear ...
Jonscher KR, Stewart MS, Alfonso-Garcia A, DeFelice BC, Wang XX, Luo Y, Levi M, Heerwagen MJ, Janssen RC, de la Houssaye BA, Wiitala E, Florey G, Jonscher RL, Potma EO, Fiehn O, Friedman JE. Early PQQ supplementation has persistent long-term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice. FASEB J. 2017 04; 31(4):1434-1448 ...
Vitamin B 12 Coenzymes use Cobamides Vitamin B 12 Deficiency Vitamin B 12-Binding Proteins use Transcobalamins ...
Cobamides--deficiency. Vitamin B 12--metabolism. Publication Types: Lecture. Webcast Download. NLM Classification: QU 194 ...
Cobamides/chemistry; Cobamides/metabolism; Corrinoids/chemistry; Corrinoids/metabolism; Ethanolamine/chemistry; Ethanolamine/ ...
Cobamides / deficiency Actions. * Search in PubMed * Search in MeSH * Add to Search ...
Cobamides / blood* Actions. * Search in PubMed * Search in MeSH * Add to Search ...
Cobamides Entry term(s). B12 Coenzymes, Vitamin Coenzymes, Vitamin B12 Deoxyadenosinecobalamins Vitamin B 12 Coenzymes Vitamin ... deficiency: coordinate COBAMIDES /defic (IM) with VITAMIN B 12 DEFICIENCY (IM). Allowable Qualifiers:. AA analogs & derivatives ... Cobamides Entry term(s):. B12 Coenzymes, Vitamin. Coenzymes, Vitamin B12. Deoxyadenosinecobalamins. Vitamin B 12 Coenzymes. ... Cobamides - Preferred Concept UI. M0004665. Preferred term. ...
Cobamides D3.549.909.437.777.270 D3.633.400.909.437.777.270 Cocaine D4.75.80.875.99.722.388 D3.605.84.500.722.388 Cochlear ...
Cobamides Preferred Concept UI. M0004665. Registry Number. 0. Terms. Cobamides Preferred Term Term UI T008811. Date01/01/1999. ... Cobamides. Tree Number(s). D03.383.129.578.840.437.777.270. D03.633.400.909.437.777.270. D04.345.783.437.777.270. D08.211.175. ... deficiency: coordinate COBAMIDES /‌defic (IM) with VITAMIN B 12 DEFICIENCY (IM). Entry Term(s). Deoxyadenosinecobalamins ...
Cobamides Preferred Concept UI. M0004665. Registry Number. 0. Terms. Cobamides Preferred Term Term UI T008811. Date01/01/1999. ... Cobamides. Tree Number(s). D03.383.129.578.840.437.777.270. D03.633.400.909.437.777.270. D04.345.783.437.777.270. D08.211.175. ... deficiency: coordinate COBAMIDES /‌defic (IM) with VITAMIN B 12 DEFICIENCY (IM). Entry Term(s). Deoxyadenosinecobalamins ...
N0000179300 Cobalamins N0000006610 Cobalt N0000166123 Cobalt Isotopes N0000166124 Cobalt Radioisotopes N0000168399 Cobamides ...
... and cobamides cofactors. This is the first report of the isolation of a methanogenic bacterium with the ability to dechlorinate ...
Cobamides D3.549.909.437.777.270 D3.633.400.909.437.777.270 Cocaine D4.75.80.875.99.722.388 D3.605.84.500.722.388 Cochlear ...
Kachadourian R, Johnson CA, Min E, Spasojevic I, Day BJ. Flavin-dependent antioxidant properties of a new series of meso-N,N-dialkyl-imidazolium substituted manganese(III) porphyrins. Biochem Pharmacol. 2004 Jan 01; 67(1):77-85 ...

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