Molybdopterin cofactor

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,... 

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. 

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). 

Synthesis of metal-organic cofactors Molybdopterin-cofactor in dehydrogenases FeMo-cofactor for nitrogenase... 

The first hint of an essential role of molybdenum in metabolism came from the discovery that animals raised on a diet deficient in molybdenum had decreased liver xanthine oxidase activity. There is no evidence that xanthine oxidase is essential for all life, but a human genetic deficiency of sulfite oxidase or of its molybdopterin coenzyme can be lethal.646,646a,b The conversion of molybdate into the molybdopterin cofactor in E. coli depends upon at least five genes.677 In Drosophila the addition of the cyanolyzable sulfur (Eq. 16-64) is the final step in formation of xanthine dehydrogenase.678 It is of interest that sulfur (S°) can be transferred from rhodanese (see Eq. 24-45), or from a related mercaptopyruvate sulfurtransferase679 into the desulfo form of xanthine oxidase to generate an active enzyme.680... 

Nicotinic acid hydroxylase from Clostridium barkerii catalyzes reaction (55), the hydroxylation of a pyridine group, and has similarities to xanthine dehydrogenase. Nicotinic acid hydroxylase is a 300 000 molecular weight flavoprotein containing iron-sulfur and FAD centres, selenium1034 and a molybdopterin cofactor.1035 Formate dehydrogenase contains selenium as selenocysteine,1036 but this does not appear to be the case for nicotinic acid hydroxylase. The possibility that the selenium is incorporated into the molybdopterin cannot be excluded at present. 

In addition to the molybdopterin cofactor, M. formicicum FDH contains a FAD molecule which is involved in hydride transfer to cofactor F420 and several [Fe-S] centers. The amino-acid sequence of the 0 subunit of FDH is 26% identical (54% similar allowing for conservative amino-acid substitutions) to the amino-acid sequence of the 0 subunit of FRH from M. (hermoautotrophicum strain AH [69]. As FRH also catalyzes hydride transfer to cofactor F420, these conserved 0-subunit sequences are likely candidates for regions involved in this common activity. There are also two clusters of four cysteine residues in the 0 subunit of FDH which appear to be arranged in a manner similar to the 2x[4Fe-4S] clusters found in bacterial and archaeal ferredoxins [123,134]. 

Mechanistic studies on the formation of the molybdopterin cofactor are still at an early stage. Conversion of guanosine, presumably as the triphosphate, to precursor Z occurs with retention of C-8 [84]. A possible mechanism for this third type of cyclohydrolase, which is consistent with the labeling experiment, is outlined in Fig. 20. (The other two types of cyclohydrolase are cyclohydrolase 1 for folate biosynthesis and cyclohydrolase II for riboflavin biosynthesis. In both cases, C8 is removed as formate.)... 

The molybdenum environment in the oxidised form of the molybdopterin cofactor of E. coli nitrate reductase A (66), and a model compound (67) for the vanadium centre in a putative vanadium-containing nitrate reductase containing an analogous cofactor. 

In biological systems Mo is present as the Fe/Mo cofactor of the nitrogenase enzymes (2) and of the multitude of oxidoreductases (3). In the latter the common molybdopterin cofactor (4), in addition to a dithiolene functionalized pyranopterin (5) ligand (Fig. 1), contains terminal oxo ligands and in the case of xanthine oxidase both oxo and thio ligands. Some aspects of molybdenum sulfur chemistry discussed in this work may be relevant to the biosynthesis of the molybdopterin cofactor and the function of xanthine oxidase (6). 

It is a monomeric (85 kDa) oxomolybdoenzyme containing three redox-active centers, including a molybdopterin cofactor and two different iron-sulfur clusters (10,11). The electron transport chain consists of the arsenite oxidase, azurin, a specific cytochrome c, and presumably a cytochrome c oxidase (10,11). 

Ferapontova, E. E., Ruzgas, T., and Gorton, L. 2003. Direct electron transfer of heme-and molybdopterin cofactor-containing chicken liver sulfite oxidase on alkanethiol-modified gold electrodes. Anal. Chem. 75 4841—1850. 

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