Molybdenum oxidoreductase

Bauder R, B Tshisuaka, F Lingens (1990) Microbial metabolism of quinoline and related compounds VII. Quinoline oxidoreductase from Pseudomonas putida a molybdenum-containing enzyme. Biol Chem Hoppe-Seyler 371 1137-1144. 

Lehmann M, Tshisuaka B, Fetzner S, Roger P, Lingens F (1994) Purification and characterization of isoquinoline 1-oxidoreductase from Pseudomonas diminuta 7, a molybdenum-containing hydroxylase. JBiol Chem 269 11254-11260. 

The oxidoreductase from Pseudomonas diminuta strain 7 that carries out hydroxylation of isoquinoline at C2 is a molybdenum enzyme containing [Fe-S] centers, which is comparable to the aldehyde oxidoreductase from Desulfovibrio gigas (Lehmann et al. 1994). 

These oxidoreductases are widely used for the introduction of the oxygen atom from HjO into heteroarenes, especially azaarenes including pyridine, quinoline, pyrimidine, and purine, and they generally contain molybdenum. 

White H, C Huber, R Feicht, H Simon (1993) On a reversible molybdenum-containing aldehyde oxidoreductase from Clostridium formicoaceticum. Arch Microbiol 159 244-249. 

De Beyer A, E Lingens (1993) Microbial metabolism of quinoline and related compounds XVI. Quinaldine oxidoreductase from Arthrobacter spec. Rii 61a a molybdenum-containing enzyme catalysing the hydroxylation at C-4 of the heterocycle. Biol Chem Eloppe-Seyler 374 101-120. 

Blase, M. Bruntner, C. Tshisuaka, B., et al., Cloning, Expression, and Sequence Analysis of the Three Genes Encoding Quinoline 2-Oxidoreductase, a Molybdenum-Containing Hydroxylase From Pseudomonas Putida 86. J, Biol Chem,. 1996. 271(38) pp. 23068-23079. 

Lehmann, M. Tshisuaka, B. Fetzner, S., et al., Purification and Characterization of Isoquinoline 1-Oxidoreductase From Pseudomonas-Diminuta-7, A Novel Molybdenum-Containing Hydroxylase. J Biol Chem, 1994. 269(15) pp. 11254-11260. 

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). 

Kroneck PMH, Aht DJ (2002) Molybdenum in nitrate reductase and nitrite oxidoreductase. In Molybdenum and Tungsten- Their Roles in Biological Processes. Sigel A, Sigel H (eds) Marcel Dekker, Inc., New York, 369-403... 

Upon purification of the XDH from C. purinolyticum, a separate Se-labeled peak appeared eluting from a DEAE sepharose column. This second peak also appeared to contain a flavin based on UV-visible spectrum. This peak did not use xanthine as a substrate for the reduction of artificial electron acceptors (2,6 dichlor-oindophenol, DCIP), and based on this altered specificity this fraction was further studied. Subsequent purification and analysis showed the enzyme complex consisted of four subunits, and contained molybdenum, iron selenium, and FAD. The most unique property of this enzyme lies in its substrate specificity. Purine, hypoxanthine (6-OH purine), and 2-OH purine were all found to serve as reductants in the presence of DCIP, yet xanthine was not a substrate at any concentration tested. The enzyme was named purine hydroxylase to differentiate it from similar enzymes that use xanthine as a substrate. To date, this is the only enzyme in the molybdenum hydroxylase family (including aldehyde oxidoreductases) that does not hydroxylate the 8-position of the purine ring. This unique substrate specificity, coupled with the studies of Andreesen on purine fermentation pathways, suggests that xanthine is the key intermediate that is broken down in a selenium-dependent purine fermentation pathway. ... 

Fe2S2] clusters are part of the molybdenum containing hydroxylases. Typically, apart from molybdenum and two EPR-distinct iron-sulfur centres there can be FAD as additional cofactor. In Chlostridium purinolyticum a selenium-dependent purine hydroxylase has been characterized as molybdenum hydroxylase. The EPR of the respective desulfo molybdenum (V) signal indicated that the Mo-ligands should differ from those of the well known mammalian corollary xanthine oxidase.197 For the bacterial molybdenum hydroxylase quinoline oxidoreductase from Pseudomonas putida an expression system was developed in order to be able to construct protein mutants for detailed analysis. EPR was used to control the correct insertion of the cofactors, specifically of the two [Fe2S2] clusters.198... 

Figure 16-31 (A) Structure of molybdopterin cytosine dinucleotide complexed with an atom of molybdenum. (B) Stereoscopic ribbon drawing of the structure of one subunit of the xanthine oxidase-related aldehyde oxidoreductase from Desulfo-vibrio gigas. Each 907-residue subunit of the homodimeric protein contains two Fe2S2 clusters visible at the top and the molybdenum-molybdopterin coenzyme buried in the center. (C) Alpha-carbon plot of portions of the protein surrounding the molybdenum-molybdopterin cytosine dinucleotide and (at the top) the two plant-ferredoxin-like Fe2S2 clusters. Each of these is held by a separate structural domain of the protein. Two additional domains bind the molybdopterin coenzyme and there is also an intermediate connecting domain. In xanthine oxidase the latter presumably has the FAD binding site which is lacking in the D. gigas enzyme. From Romao et al.633 Courtesy of R. Huber.

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... 

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