DMSO reductase family

However, some of these structures show unusual features and a crowded active site. EXAFS studies of Rhodobacter capsulatus DM SO reductase show the expected four Mo-S ligands and one Mo-O bond arising from a serine residue plus one Mo=0 in the reduced Mo (IV) state of the active site. This oxo ligand is removed upon oxidation of the metal ion to Mo(VI). In the oxidized structme, an aquo ligand is postulated to coordinate the molybdenum ion (Fig. 11.17c) [126-128]. An equivalent restdt has been reported for BSO that catalyzes the reduction of D-biotin D-sulfoxide to D-biotin [129]. A similar overall catalytic mechanism is expected for nitrate reductases (Fig. 11.18), which catalyze the following reaction  

These enzymes are present in both eukaryotes and prokaryotes and play an important role in nitrogen assimilation and dissimilation [130, 131]. Crystal structures have been reported for the monomeric NR from Desulfovibrio desuljuri-cans [119] and the heterodimeric enzyme from R. sphaeroides [120]. The former contains Mo bound to the bis(MGD) cofactor and a [Fe4SJ cluster separated by about 12 A [119]. The large subunit of the dimeric enzyme is homologous to the D. suljuricans enzyme whereas its small subunit contains two c-type hemes that act as electron transfer units [120]. As in oxidized DMSO reductase, the Mo ion is coordinated by the four thiolates from the bis(MGD) cofactor, a protein side chain (cysteine in this case) and a hydroxo/water ligand. Consequently, the proposed catalytic mechanism is similar to the one advanced for DMSO reductase [119]. 

XOR accelerates the hydroxylation of purines, pyrimidines, pterins and aldehydes [132]. In humans, the enzyme catalyzes the last two steps of purine catabolism the oxidation of hypoxanthine to xanthine and of the latter to uric acid. An unusual property of this, but not aU XOR enzymes [133], is its interconversion between xanthine dehydrogenase and xanthine oxidase activities which implies a switch between NAD and molecular oxygen being used as the final electron acceptor [134]. Structural studies suggest that this switch, that can be irreversibly induced by proteolysis [135], results from conformational changes that lead to both restricted access to the NAD cofactor to its binding site and changes in the redox potential of the FAD cofactor [136], 

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McEwan AG, IP Ridge, CA McDevitt, P Hugenholtz (2002) The DMSO reductase family of microbial molybdenum enzymes molecular properties and the role in the dissimilatory reduction of toxic elements. 

III. DMSO-reductase family (bacterial DMSO reductase DMSO to DMS... 

In the case of the DMSO reductase family, as pointed out above, the metal centre is bound to two molecules of the cofactor. DMSO reductase itself catalyses the reduction of dimethylsulfoxide to dimethylsulfide with incorporation of the oxygen atom of DMSO into water. The active site of the oxidized enzyme is an L2MoVI0(0-Ser) centre, which, upon reduction, loses the M=0 ligand to give a L2MoIV(0-Ser) centre. In the catalytic... 

A number of other reductases and dehydrogenases, including dissimilatory nitrate reductases of E. coli and of denitrifying bacteria (Chapter 18), belong to the DMSO reductase family. Other members are reductases for biotin S-oxide,649 trimethylamine N-oxide, and polysulfides as well as formate dehydrogenases (Eq. 16-63), formylmethanofuran dehydrogenase (Fig. 15-22,... 

The active site structures of the three classes of molybdenum-containing enzymes are compared in Fig. 16-32. In the DMSO reductase family there are two identical molybdopterin dinucleotide coenzymes complexed with one molybdenum. However, only one of these appears to be functionally linked to the Fe2S2 center. 

The bis(l,2-enedithiolate) complexes discussed closely resemble the metal centers found in the dmso reductase family of Mo enzymes and in the tungsten enzymes. The reactivity of mono(l,2-enedithiolate) complexes remains a continuing challenge as synthetic chemists pursue accurate models for the xanthine oxidase and sulfite oxidase families of metal sites. New 1,2-dithiolate ligands [70,71] and complexes are needed to demonstrate ligand effects to help elucidation reaction mechanism. 

DMSO Reductase Family DMSO reductase R. sphaeroides a, 85 MoO(OSer)(MGD)2 Mc2SO — Mc2S lEUl... 

The enzymes are subdivided into three families based on structural and sequence comparisons (Figure 1, Table 1). Oxotransferases isolated from prokaryotes (see Prokaryote) belong to the DMSO reductase family. These enzymes include DMSO reductase, biotin X-oxide reductase, trimethylamine A-oxide reductase, dissimilatory nitrate reductase, formate... 

Alcaligenes faecalis and five members of the p Proteobacteria are heterotrophic arsenite oxidizers, whereas Pseudomonas arsenitoxidans and NT-26 grew anaerobically through chemoautotrophic oxidation (Oremland and Stolz, 2005 Santini et al, 2000). However, six members of a Proteobacteria (Ben-5, NT-3, NT-4, NT-2, NT-26, and NT-25) and one member of y Proteobacteria (MLHE-1) were known chemohthoautotrophic arsenite oxidizers (Oremland et al, 2002). The best characterized and probably most studied of aU arsenite oxidizers is Alcaligenes faecalis, a heterotrophic arsenite oxidizer (Osborne and Enrlich, 1976). The arsenite oxidase from Alcaligenes faecalis has been purified and structurally characterized (Ellis et al, 2001). A similar enzyme has also been purified from the heterotrophic arsenite oxidizers Hydrogenophaga sp. strain NT-14 (Vanden Hoven and Santini, 2004) and the chemolithoautotrophic Rhizobium sp. strain NT-26 (Santini and Vanden Hoven, 2004), which indicate that the arsenite oxidase enzyme is also a member of the DMSO reductase family of molybdenum enzymes, similar to the respiratory arsenate reductases (Arr). The arsenite oxidase heterodimer comprises an 88 kDa catalytic subunit encoded by the aoxB gene that contains a [3Fe-4S] cluster and molybdenum bound to the pyranopterin cofactor and a 14 kDa subunit... 

The bis-dithiolene complexes of both molybdenum and tungsten have been the best characterized family structurally as well as their kinetics for OAT reactions, making the DMSO reductase family the easiest to mimic chemically. However, well-characterized bis-dithiolene complexes are those featuring Mo,v(0) and MoVIfO)2 moieties (as illustrated in Figure 3.16). Exact structural analogues of the minimal DMSO reductase active sites, that is desoxo Mofv, have been realized (Figure 3.17). However, the study of their OAT kinetics has been complicated by the fact that monooxo MoVI(0) complexes are unstable and decompose rapidly to monooxo Mov... 

Figure 16 The biosynthesis of Moco and bis-MGD. Shown is a scheme of the biosynthetic pathway for Moco biosynthesis in bacteria and eukaryotes. The proteins involved in the reactions are colored in red for bacterial proteins and blue for human proteins. In bacteria, Moco (54) can be further modified by the attachment of, for example, GMP, forming MGD, and two equivalents of MGDare bound to molybdenum, forming the so-called bis-MGD cofactor (56). Further, Moco can be modified by the replacement of one 0x0 ligand by a sulfido ligand, forming the monooxo Moco (55). The three molybdenum containing enzyme families are divided into the xanthine oxidase, sulfite oxidase, and DMSO reductase families according to their active site structures.

The DMSO Reductase Family (LjMoX-Possessing Enzymes)... 

DMSO Reductase Family The DMSO reductase family consists of a number of molybdenum enzymes, all from bacterial and archaeal sources, that exhibit substantial sequence homology which justifies their being grouped into a single family. DMSO reductase, which may be isolated from the periplasmic space of Rhodobacter sp., catalyzes the reductive desoxygenation of DMSO to dimethylsulfide (Hille 1996). 

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