The Molybdenum Cofactor Mo-co

The review by Rajagopalan (19) provides a detailed analysis of the genetics and biochemistry of the molybdenum cofactor, as well as an excellent historical account of the experiments that led to the present view of this entity. Here we briefly outline this history and the current status of chemical approaches to understanding Mo-co. 

In the early 1970s Nason and co-workers showed that extracts of nit-1 mutants of Neurospora crassa exhibited nitrate reductase activity when mixed with solutions of other molybdenum enzymes that had been subjected to denaturing conditions (20-23). The isolation and 

Deistung and Bray (29) have described a procedure for anaerobic isolation of active intact molybdenum cofactor from xanthine oxidase. The molecular mass by gel filtration was about 610. Hawkes and Bray (30) have reported that Mo-co from xanthine oxidase and sulfite oxidase can be stabilized under anaerobic conditions in the presence of dithio-nite and that oxidation in the presence of thiophenol results in EPR signals characteristic of Mo(V) and little loss of cofactor activity (31). However, to date intact Mo-co has not been structurally characterized. The possible coordination about the molybdenum atom in Mo-co in enzymes is discussed in Section III. 

Molybdopterin itself is also extremely unstable when released from a protein and has never been structurally characterized in its native state (32, 33). Mass spectral and NMR studies of the difcarboxamido-methyl) derivative of the oxidized form of molybdopterin have provided convincing evidence that this derivative is a 6-substituted pterin that possesses structure 3 (34). A 6-substituted pterin moiety now appears to be a common feature of all of the molybdenum enzymes of Table I. There is still some question about the oxidation state of the pterin ring 

The proposed dithiolene structure in the side chain of 1-3 is unusual for a naturally occurring compound and is still the subject of some controversy. Curtius et al. (37) have pointed out that a tetrahydropterin ring system possessing an unsaturated (dithiolene) side chain in the 6-position (e.g., 5a) is a redox tautomer of 5b, a structure with a satu- 

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Note that molybdopterin is the organic component of the molybdenum cofactor (Mo-co) and contains no molybdenum. Frequently molybdopterin is incorrectly equated to Mo-co. 

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