Dimethylbenzimidazole ligand

Base-off, his-on means that the 5,6-dimethylbenzimidazole ligand (cf. Fig. 1) is detached and replaced by a histidine residue from the protein partner base-on means that the 5,6-dimethylbenzimidazole ligand is still ligated to cobalt. 

Thusius has studied the kinetics of cobalamin-ligand substitution reactions trans to the pendant 5,6-dimethylbenzimidazole ligand (Eqn. 59) for a variety of inorganic ligands including thiocyanate, azide, iodide and bromide ions [103]. 

Fig. 1. Structure of 5 -deoxyadenosylcobalamin (coenzyme B12). The reactive cobalt CH2-bond is marked. In pseudocoenzyme B12 the lower dimethylbenzimidazole ligand is replaced by adenine (lower right)...

The Preparation and Characterization of Organocobalt(III) Complexes of the General Formula [RCo" (L )X] where L4 is the equatorial ligand (Corrin, etc.) and X is the unidentate axial ligand (.S,6-dimethylbenzimidazole, HjO or absent, where L is corrin otherwise as stated in the table). 

Complexes with 1,2-dimethylbenzimidazole have been described, and there is evidence that the ligand may act as both a monodentate and a bidentate N donor.432 The ligand (55) is... 

As shown in Figure 10.12, four of the six chelation sites of the cobalt atom of cobalamin are occupied by the nitrogens of the corrin ring and one by the nitrogen of the dimethylbenzimidazole side chain. The sixth site may be occupied by the following ligands in biologically active vitamers ... 

Lawrence, C. C., Gerfen, G. J., Samano, V., Nitsche, R., Robins, M. J., and Stubbe, J., 1999, Binding of Cob(II)alamin to the adenosylcobalamin-dependent ribonucleotide reductase from Lactobacillus leichmanniioldentification of dimethylbenzimidazole as the axial ligand, J. Biol. Chem. 274 7039n7042. 

The corrin ligand and the basic motif of the nucleotide chain are widely conserved structural units in the natural corrins. Norpseudovitamin B12 (8) is the first example of a natural corrinoid with a modified isopropanolamine linker it is (the isolation form of) the cofactor of perchloroethene-dehalogenase in an obligate anaerobe. The nucleotide bases (a 5,6-dimethylbenzimidazole in the cobalamins) of natural complete corrins from different bacterial sources also exhibit variability in their constitution (Figure 2). ... 

Figure 1 In the above structure, R = CN denotes cyanocobalamin (CN-Cbl), whilst R = OH is hydroxocobalamin (OH-Cbl) R = 5 -deoxyadenosyl is coenzyme B12 (adenosylcobalamin, AdoCbl) and R = Me is methylcobalamin (MeCbl). By definition all cobalamins contain 5,6-dimethylbenzimidazole, which is the so-called 6th ligand to cobalt in the above structure. Substances containing the corrin ligand, i.e. the planar 14 electron p-system embracing cobalt in the above structure, are also called corrinoids.

Gray MJ, Escalante-Semerena JC. Single-enzyme conversion of FMNH2 to 5,6-dimethylbenzimidazole, the ligand of B12. Proc. Natl. Acad. Sci. U.S.A. 2007 104 2921-2926. 

We were interested in the specificity of methyl corrinoid derivatives and tested methyl factor III and methyl factor B as substrates for methane formation. Specificity for activation of the methyl group did not reside in the lower axial ligand since the methyl group was converted readily to methane in the absence of the dimethylbenzimidazole moiety of the lower axial ligand (11). 

FIGURE 16.15. Proposed movement of a free radical when the Co-C bond is broken in a Bi2 coenzyme (Ref. 78). The Co +-C bond is broken and the adenosyl radical moves to the active site of the enzyme bound to the B12 cofactor. The lower axial ligand, the 5,6-dimethylbenzimidazole, can also swing away, but is constrained in its pathway by the sidechains 20, 30, 41, and 48. In a similar way the path of the adenosyl group is controlled by the sidechains 26, 37, 46, and 54. 

Vitamin B12 (cyanocobalamin) 3 is, in fact, not a natural product as the cyanide ligand to the cobalt ion is added during the isolation procedure. Coenzyme B12 (adenosylcobalamin) 4 and methylcobalamin 5 are the true final products of the biosynthetic pathway. Coenzyme 0,2 is the cofactor for a number of enzymic rearrangement reactions, such as that catalysed by methylmalonyl CoA mutase, and methylcobalamin is the cofactor for certain methyl transfer reactions, including the synthesis of methionine. A number of anaerobic bacteria produce related corrinoids in which the dimethylbenzimidazole moiety of the cobalamins (3 - 5) is replaced by other groups which may or may not act as ligands to the cobalt ion, such as adenine orp-cresol [12]. 

There is substantial literature on cobalt-containing compounds in which a carbon-cobalt bond is in an axial position trans to usually an N-donor ligand, with the four equatorial positions occupied by N-donors too. This coordination arrangement is present in adenosylcobalamin (AdoCbl, coenzyme B12) and in cyanocobalamin (CNCbl, vitamin B12). The trans N-donor is dimethylbenzimidazole (DMBz) attached to a nucleotide (Scheme 2). 

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