Molybdopterines

The properties of CODH/acetyl-CoA synthase are summarized in Table II. The enzyme has been isolated from eight species. There exist three types of CODH. One, which lacks nickel and acetyl-CoA synthase activity, contains a molybdopterin active site and will not be... 

The three known crystal structures of molybdopterin-containing enzymes are from members of the first two families the aldehyde oxido-reductase from D. gigas (MOP) belongs to the xanthine oxidase family (199, 200), whereas the DMSO reductases from Rhodobacter (R.) cap-sulatus (201) and from/ , sphaeroides (202) and the formate dehydrogenase from E. coli (203) are all members of the second family of enzymes. There is a preliminary report of the X-ray structure for enzymes of the sulfite oxidase family (204). 

The aldehyde oxidoreductase from Desulfovibrio gigas shows 52% sequence identity with xanthine oxidase (199, 212) and is, so far, the single representative of the xanthine oxidase family. The 3D structure of MOP was analyzed at 1.8 A resolution in several states oxidized, reduced, desulfo and sulfo forms, and alcohol-bound (200), which has allowed more precise definition of the metal coordination site and contributed to the understanding of its role in catalysis. The overall structure, composed of a single polypeptide of 907 amino acid residues, is organized into four domains two N-terminus smaller domains, which bind the two types of [2Fe-2S] centers and two much larger domains, which harbor the molybdopterin cofactor, deeply buried in the molecule (Fig. 10). The pterin cofactor is present as a cytosine dinucleotide (MCD) and is 15 A away from the molecular surface,... 

The protein from D. desulfuricans has been characterized by Mbss-bauer and EPR spectroscopy 224). The enzyme has a molecular mass of approximately 150 kDa (three different subunits 88, 29, and 16 kDa) and contains three different types of redox-active centers four c-type hemes, nonheme iron arranged as two [4Fe-4S] centers, and a molybdopterin site (Mo-bound to two MGD). Selenium was also chemically detected. The enzyme specific activity is 78 units per mg of protein. 

The degradation of isoquinoline by Pseudomonas diminuta strain 7 is initiated by an oxidoreductase that contains [2Fe-2S] centers and the cofactor molybdopterin cytosine dinucleotide (Lehmann et al. 1994). 

Acetylene hydratase from the anaerobe Pelobacter acetylenicus is a tungsten-iron-sulfur enzyme that resembles molybdopterin with W replacing Mo (Meckenstock et al. 1999), and catalyzes the addition of the elements of water to acetylene (Figure 3.30a). 

Hetterich D, B Peschke, B Tshisuaka, F Lingens (1991) Microbial metabolism of quinoline and related compounds. X. The molybdopterin cofactors of quinoline oxidoreductases from Pseudomonas putida 86 and Rhodococcus sp. B1 and of xanthine dehydrogenase from Pseudomonas putida 86. Biol Chem Hoppe-Seyler 372 513-517. 

The carbon monoxide dehydrogenase of the aerobe Oligotropha carboxidovorans contains both Cu and Mo in the form of a cluster in which the Mo is bound to the thiol groups of molybdopterin cytosine nucleotide, and the Cu to cysteine residue in the form of a Cu-S-Mo(=0)OFl cluster (Dobbek et al. 2002). 

Molybdopterin is a component of four enzyme families all of which contain Mo(VI) the xanthine oxidase and the sulfite oxidase families with one molybdopterin and the DMSO family with two molybdopterins. There are a number of tungsten-containing enzymes with structures analogous... 

FIGURE 3.37 Structure of molybdopterin conjugated with cytidine diphosphate. 

They have a molecular mass of 300-360 kDa, and contain per molecule, eight atoms of Fe, eight atoms of acid-labile S, two atoms of Mo, and two molecules of FAD. The organic component of the pterin molybdenum cofactor is generally molybdopterin cytosine dinucleotide (Hetterich et al. 1991 Schach et al. 1995). 

Tungsten-containing enzymes have been found to mediate a variety of reactions both in aerobic and anaerobic bacteria, and their structure may plausibly be assumed to be analogous to the molybdopterins ... 

Boyington JC, VN Gladyshev, SV Khangulov, TC Stadtman, PD Sun (1997) Crystal structure of formate dehydrogenase H catalysis involving Mo, molybdopterin, selenocysteine, and an Fe4S4 cluster. Science 275 1305-1308. 

Llamas A, RR Mendel, G Schwarz (2004) Synthesis of adenylated molybdopterin. An essential step for molybdenum insertion. J Biol Chem 279 55241-55246. 

Reichenbecher W, A Rudiger, PMH Kroneck, B Schink (1996) One molecule of molybdopterin guanine dinucleotide is associated with each subunit of the heterodimeric Mo-Fe-S protein transhydroxylase of Pelobacter acidigalUci as determined by SDS (PAGE) and mass spectrometry. Eur J Biochem 237 406-413. 

Xanthine oxidoreductase (XOR) is a molybdenum-containing complex homodimeric 300-kDa cytosolic enzyme. Each subunit contains a molybdopterin cofactor, two nonidentical iron-sulfur centers, and FAD (89). The enzyme has an important physiologic role in the oxidative metabolism of purines, e.g., it catalyzes the sequence of reactions that convert hypoxanthine to xanthine then to uric acid (Fig. 4.36). 

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