Pterins molybdenum enzymes

Mononuclear molybdenum pterine-based enzymes 96CRV2757. 

DNA cleavage by, 43 158-159 reactions, copper proteins, 39 25 Oxo-trichloroselenates(IV), 35 270-271 Oxo-type molybdenum enzyme, see Molybdenum enzymes, pterin-containing Oxovandium (IV), solvent exchange and ligand substitution, 42 47-49 Oxyanions, Groups VIB and VIIB, redox reactions, kinetics and mechanism, 40 269-274... 

Wootton, J.C., Nicolson, R.E., Cock, J.M., Walters, D.E., Burke, J.F., Doyle, W.A. Bray, R.C. (1991). Enzymes depending on the pterin molybdenum cofactor sequence families, spectroscopic properties of molybdenum and possible cofactor-binding domains. Bio-chimica et Biophysica Acta 1057, 157-85. 

The evidence for a pterin-substituted 1,2-enedithiolate was first reported by Raja-gopalan, Johnson, and coworkers, who isolated pterins from the oxidative decomposition of molybdenum-bound MPT, Figure 4 [7,49,55,56], In complementary work, Taylor and coworkers confirmed the structure of several of the pterin decomposition products by direct synthesis (see Section V. A) [30,57-59], Urothi-one, first isolated in 1940 from human urine [60], was shown to be a metabolic degradation product of MPT [37], Other isolated pterin-containing decomposition and/or derivatized products from molybdenum enzymes include Form A, Form B (a urothione-like product), and camMPT (Figure 4) [7], Two other pterins, Form Z and the MPT precursor, can be obtained from molybdenum deprived organisms, N. crassa Nit-1, and oxidase-deficient children, neither of which pro-... 

The molybdenum-containing oxidoreductases that catalyze Eq. (1) have been variously termed molybdenum hydroxylases (6), oxotransferases (7), and oxo-type molybdenum enzymes (8). Molybdenum hydroxylase aptly describes the conversion of xanthine to uric acid, but the name seems less appropriate for the reactions catalyzed by sulfite oxidase and nitrate reductase oxotransferase implies that the function of these enzymes is to transfer oxo groups, even though relatively little is known about their actual mechanism of action and the name oxo-type molybdenum enzyme recognizes both the apparent oxo transfer chemistry of Eq. (1) and the fact that the molybdenum atom in each of these enzymes contains at least one terminal oxo group. In this chapter, we shall refer to these enzymes as pterin-containing molybdenum enzymes because a 6-substituted pterin appears to be a common chemical feature of all of the enzymes. 

The chapter consists of nine sections. Sections II through VII deal with the pterin-containing molybdenum enzymes. Biochemical and model studies of molybdopterin, Mo-co, and related species are described in Section II. In Section III, we briefly survey physical and spectroscopic techniques employed in the study of the enzymes, and consider their impact upon the current understanding of the coordination about the molybdenum atom in sulfite oxidase and xanthine oxidase. Model studies are described in Sections IV and V. Section IV concentrates on structural and spectroscopic models, whereas Section V considers aspects of the reactivity of model and enzyme systems. The xanthine oxidase cycle (Section VI) and facets of intramolecular electron transfer in molybdenum enzymes (Section VII) are then treated. Section VIII describes the pterin-containing tungsten enzymes and the evolving model chemistry thereof Future directions are addressed in Section IX. 

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... 

In summary, a 6-substituted pterin was first identified as a structural component of the molybdenum cofactor from sulfite oxidase, xanthine oxidase and nitrate reductase in 1980 (24). Subsequent studies provided good evidence that these enzymes possessed the same unstable molyb-dopterin (1), and it seemed likely that 1 was a constituent of all of the enzymes of Table I. It now appears that there is a family of closely related 6-substituted pterins that may differ in the oxidation state of the pterin ring, the stereochemistry of the dihydropterin ring, the tautomeric form of the side chain, and the presence and nature of a dinucleotide in the side chain. In some ways the variations that are being discovered for the pterin units of molybdenum enzymes are beginning to parallel the known complexity of naturally occurring porphyrins, which may have several possible side chains, various isomers of such side chains, and a partially reduced porphyrin skeleton (46). 

The characteristic fluorescence spectra of oxidized pterins observed in solutions of denatured molybdenum enzymes provided some of the first clues that the molybdenum cofactor contains a pterin unit (24). 

The postulated catalytic cycles for pterin-containing molybdenum enzymes involve a two-electron change at the molybdenum atom (Mo(VI) Mo(IV)). Microcoulometric titrations of nitrate reductase Chlorella vulgaris) (76), milk xanthine oxidase (77), and sulfite oxidase (78) show that their molybdenum centers are reduced by two electrons. The reduction potentials for the molybdenum center of chicken liver sulfite oxidase are strongly dependent upon pH and upon anion concentration (78). 

As mentioned above, tungsten enzymes are found in place of molybdenum enzymes in thermophilic bacteria and hyperhermophilic archaebacteria. Like the molybdenum enzymes, they can be classified into three broad families, all of which contain two pterin cofactor molecules per Mo. In this respect, they are similar to the DMSO reductase... 

DMSO) reductase and biotin-S-oxidoreduc-tase, as well as the bacterial dissimilatory (or respiratory) nitrate reductases (Hille 1996) (Table 18.8). The mononuclear molybdenum enzymes possess a pterin cofactor and may be categorized based on the structure of their molybdenum center... 

The pterin-containing molybdenum enzymes catalyze particularly the oxidation ofC-H compounds [56, 57], For example, xanthine oxidase transforms xanthine into uric acid according to the equation ... 

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