Molybdenum and tungsten enzymes

Bioinorganic Chemistry of Pterin-Containing Molybdenum and Tungsten Enzymes John H. Enemark and Charles G. Young... 

Me Master, J. and Enemark, J.H. (1998). The active sites of molybdenum and tungsten enzymes. Curr. Opin. Chem. Biol., 2, 201-207... 

Another factor that characterizes molybdenum and tungsten enzymes is that instead of using the metal itself, directly coordinated to amino acid side-chains of the protein, an unusual pterin cofactor, Moco, is involved in both molybdenum- and tungsten-containing enzymes. The cofactor (pyranopterin-dithiolate) coordinates the metal ion via a dithiolate side-chain (Figure 17.2). In eukaryotes, the pterin side-chain has a terminal phosphate group, whereas in prokaryotes, the cofactor (R in Figure 17.2) is often a dinucleotide. 

Brondino, C.D., Romao, M.J., Moura, I. and Moura, J J.G. (2006) Molybdenum and tungsten enzymes the xanthine oxidase family, Curr. Opin. Chem. Biol., 10, 109-114. 

ScHiNDELiN, H., Kisker, C., and Rajagopalan, K. V. Molybdopterin from molybdenum and tungsten enzymes, Adv Protein Chem 2001, 58,... 

I. INTRODUCTION THE MOLYBDENUM AND TUNGSTEN ENZYMES, A BIOLOGICAL PERSPECTIVE... 

In the last 5 years, 20 new enzymes have been confirmed to contain either molybdenum or tungsten, and in the last 3 years representive members of both molybdenum and tungsten enzyme families have been crystallographically characterized. 

There are several recent reviews of the molybdenum and tungsten enzymes [4-6,23,26-36], In this chapter, we first define the metallocofactors and offer a compilation of the enzymes and their diverse activities. We then focus on the active-site structures, highlighting the confluence of crystallographic and spectroscopic studies. This is followed by a discussion of pertainent spectroscopic, structural, reactivity, and theoretical model studies. We then turn our attention to the mechanisms of catalytic activity of the molybdenum and tungsten enzymes. 

From recent x-ray crystallographic studies of both molybdenum and tungsten enzymes, MPT is now known to be a C(6)-substituted 5,6-dihydropterin that is covalently alkoxylated at the C(7) position by the alcohol of the 1,2-enedithio-late side chain (Eq. 1) [39],... 

Figure 2 The structures ofthe MPT cofactor subfamilies. The boxes represent subfamilies of molybdenum and tungsten enzymes with high sequence homology. Cofactor structure type determined aby x-ray crystallography from the listed source bby EXAFS.

Figure 3 The reconstitution of aponitrate reductase from the Nit-1 Neurospora crassa mutant by MPT-containing extracts from the molybdenum and tungsten enzymes.

The enzymes that catalyze substrate oxidation are oxidases, hydroxylases, dehydrogenases, and oxidoreductases. Most of the substrate oxidations catalyzed by molybdenum and tungsten enzymes involve the net transfer of an oxygen atom... 

Table 1c Molybdenum and Tungsten Enzyme Catalyzed Oxidations and Reductions of Oxygen-Bearing Carbon Centers...

Table 2e Non-redox Processes Catalyzed by Molybdenum and Tungsten Enzymes...

Although molybdenum and tungsten enzymes carry the name of a single substrate, they are often not as selective as this nomenclature suggests. Many of the enzymes process more than one substrate, both in vivo and in vitro. Several enzymes can function as both oxidases and reductases, for example, xanthine oxidases not only oxidize purines but can deoxygenate amine N-oxides [82]. There are also sets of enzymes that catalyze the same reaction but in opposite directions. These enzymes include aldehyde and formate oxidases/carboxylic acid reductase [31,75] and nitrate reductase/nitrite oxidase [83-87]. These complementary enzymes have considerable sequence homology, and the direction of the preferred catalytic reaction depends on the electrochemical reduction potentials of the redox partners that have evolved to couple the reactions to cellular redox systems and metabolic requirements. 

Chemical systems of relevance to the molybdenum and tungsten enzymes include synthetic pterins, a-phosphorylated ketones (as precursor models), and a variety of molybdenum and tungsten oxido, sulfido, and 1,2-enedithiolate complexes. These compounds have been used to (1) confirm the identity of MPT derivatives (2) define steps in MPT biosynthesis (3) calibrate spectroscopic observations (4) give precise geometries and reactivities that can be used as input for theoretical studies and (5) provide options for mechanistic consideration. 

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