Corrins cofactors

As we will see in subsequent chapters, many metalloproteins have their metal centres located in organic cofactors (Lippard and Berg, 1994), such as the tetrapyrrole porphyrins and corrins, or in metal clusters, such as the Fe-S clusters in Fe-S proteins or the FeMo-cofactor of nitrogenase. Here we discuss briefly how metals are incorporated into porphyrins and corrins to form haem and other metallated tetrapyrroles, how Fe-S clusters are synthesized and how copper is inserted into superoxide dismutase. 

Corphin is the F-430 cofactor found in methyl-coenzyme M reductase, a nickel-containing enzyme that participates in the conversion of carbon dioxide to methane in methanogenic bacteria. The nickel ion in F-430 is coordinated by the tetrahydrocorphin ligand, which contains structural elements of both porphyrins and corrins. 

A tetrapyrrole (related to porphyrins and corrins) containing a nickel ion. This cofactor, corphin, is a crucial component of methyl-coenzyme M reductase, a bacterial enzyme participating in the formation of methane. 

Coenzyme B12 is the cofactor form of vitamin B 2, which is unique among all the vitamins in that it contains not only a complex organic molecule but an essential trace element, cobalt. The complex corrin ring system of vitamin B12 (colored blue in Fig. 2), to which cobalt (as Co3+) is coordinated, is chemically related to the porphyrin ring system of heme and heme proteins (see Fig. 5-1). A fifth coordination position of cobalt is filled by dimethylbenzimidazole ribonucleotide (shaded yellow), bound covalently by its 3 -phosphate group to a side chain of the corrin ring, through aminoisopropanol. 

Eschenmoser [15] has recently alluded to the concepts of structure-directed synthesis and autochthonous reactivity — the propensity of certain systems to undergo reactions as a consequence of their intrinsic molecular structural factors — within the context of certain biomolecules, particularly the organic cofactor, vitamin B12. The formation of the AD ring junction in the corrin ligand had to be regarded as a major hurdle in any proposed chemical synthesis of cobyric acid (5) (Fig. 2), and hence of vitamin B12. However, driven initially by the desire to identify a dark, and therefore potentially biomimetic, variant of the photochemical... 

Reitzer et al., 1999) and a MeCbl-binding fragment of E. coli methionine synthase (Drennan et al., 1994), the cofactor is sandwiched between two domains (Figure 8). The conserved domain possesses an a/ 3 structure reminiscent of the Rossmann fold of nucleotide-binding proteins (Rossmann et al., 1974) and consists of a twisted )-sheet of five parallel strands encased by five a-helices. It binds the lower, a-face of the corrin macrocycle and the substituents projecting idowni from this face, notably the dimethylbenz-imidazole ribofuranosyl nucleotide loop. 

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). ... 

The cofactor role of the methylcorrinoids is based on enzymatic methyl-group transfer reactions. Formation of a methyl-corrin by the methylation of an enzyme-bound Co -corrin... 

The common structural element is the macrocyclic corrin ring that holds Co in a square-planar coordination geometry as shown in Fig. 15-1(a) [1] The form that is a cofactor for methyl transferase reactions is MetCbl, the form that is a cofactor for about a dozen enzymes that catalyse 1,2-migrations is AdoCbl , and the form found in... 

Vitamin B12 contains cobalt in a corrin ring that resembles a porphyrin. In the cofactor forms of the vitamin, an adenosyl moiety or methyl group is attached to the cobalt, forming adenosylcobalamin or methylcobalamin (Figure 7-17). 

The other type of radical chemistry of importance in the carbohydrate field is one-electron reductions. A handful of these reactions (such as the metallic Zn reduction of acetobromoglucose to triacetylglucal) have been used in synthesis for decades, but, starting with the Barton-McCombie deoxygenation of sugars in the mid-1970s there has been an explosion of interest, as increasingly sophisticated cascades of elementary radical steps have been devised. Such reactions are driven by the homolysis of weak bonds such as Sn-H or N-O under conditions of photolysis or mild thermolysis. Nature uses a similar basic principle in Type II ribonucleotide reductases, where the weak bond in question is the cobalt-carbon a bond in the corrin cofactor. ... 

N., Banerjee, R., Spiro, T. G. (1998) Resonance Raman spectra of methylmalonyl-Coenzyme A mutase, a coenzyme Bi2-dependent enzyme, reveal dramatic change in corrin ring conformation but little change in Co-C bond force constant in the cofactor upon its binding to the enzyme, J. Am. Chem. Soc. 120, 9947-9948. 

Vitamin B12 and its active form coenzyme, (5 -deoxyadenosylcobalamin), are tetrapyrrole-based cobalt-containing macrocyclic complexes containing the 15-membered corrin ring. They act in concert with an apoenzyme (a large protein that binds simultaneously the cofactor and the substrate in order to carry out a variety of mutase enzymatic transformations, generally involving radical-based... 

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