Cobamide structure

B23. Barker, H., Structure and function of cobamide coenzymes. Federation Proc. 20, 956-961 (1961). 

Figure 1 Representative structural formulae and corresponding symbols of cobalamins([5, 6 -dimethylbenzunidazolyl]cobamides, (a)) and of diaquo-Co forms of incomplete corrins (b)...

Figure 28 Chemical structure of archaeal cobamide factor III.

Due to the discovery of the replacement of the cobalt coordinated 5,6-dimethylimidazole (DMB) base by a protein-derived imidazole in several Bi2-dependent enzymes (see later), the analysis of Co -cyano-imidazolylcob-amide (8) [31] was of particular interest. The less bulky and more nucleophilic imidazole base of 8 caused a number of structural differences. The corrin ring fold angle of 8 decreased to 11.3° and the axial Co-N bond shortened (from 2.011 A in 1 to 1.968 A in 8). In addition, the base tilt of 8 (i.e., half the difference between the two Co - N - C angles to the coordinating base) decreased to practically zero, within experimental error. In all crystal structures of 5, 6 -dimethylbenzimidazoyl-cobamides a tilt of about 5° is found [36], which appears to be an inherent property of the cobalt-coordinated DMB. 

A major factor in the importance of heteronuclear NMR spectroscopy is that the structures (in solution) of noncrystalUne B12 derivatives can be characterized. One of the main examples of this is the natural complete but base-off protonated form of coenzyme B12 (2-H ) [79]. More recently, the solution structures of the organometaUic derivatives pseudocoenzyme B12 (37), adenosyl-factor A (38) [76] and neocoenzyme B12 (39) [83] could be analyzed in great detail. The structures and the base-on/base-off equilibria of a range of protonated base-off cobamides have also been investigated in aqueous solution [74,77]. 

The crystallographic results on the structure of MetH and the finding of the base-off/His-on binding of the cofactor in a Bi2-dependent methyl transferase were consistent with earlier ESR spectroscopic evidence for histidine binding to the cobalt center of p-cresolyl-cobamide (52) in the aceto-gen Sporomusa ovata [145,169]. Various other B -dependent methyltrans-ferases are indicated to have either a base-off/His-on bound methyl-Co(III)-corrinoid, or even a methyl-corrinoid cofactor in base-off form (where His-coordination is absent) [156]. 

The x-ray analysis of MMCM was the first crystal structure of a coenzyme B12-dependent enzyme [18,163,194,195]. The study concerned the 150 kDa heterodimeric MMCM from P. shermanii and showed the B -cofactor to be bound base-off/His-on. The a-side of the corrin-bound cobalt center was coordinated to the histidine of the regulatory triad His-Asp-Lys. As in MetH the nucleotide tail of the boimd corrinoid was tightly inserted into the protein and the corrinoid was boimd at an interface between two domains. A rather flat corrin ligand with a ligand-folding comparable to that in imidazolyl-cobamides was revealed [31,68]. 

Three crystal structures of DD [20,217,219] and two of GD [215,220] have been studied, confirming the base-on nature of the boimd corrinoid. Analysis of the crystal structure of DD reconstituted with the coenzyme B12 analogue 5-adeninyl-pentyl-cobalamin (53) [217] helped identify an adenine-binding pocket in the substrate-binding a-subunit. The observed mode of adenine binding allowed the inference of a build-up of strain in the bound adenosyl-cobamide cofactor and activation towards homolysis of the Co - C bond. 

The structure of vitamin B12 was estabhshed as -(5,6-dimethylbenzimid-azolyl)cobamide cyanide (I) by chemical degradation and physical methods, particularly including X-ray crystallography. Details of these structural studies may be found in several reviews - . 

Vitamin B12 chemistry. The structure of the 5,6-dimethylbenzimidazole-cobamide-coenzyme, as found in the wet crystals, has been determined by X-ray and neutron diffraction (see Figure 59) [123, 124]. A schematic... 

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