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Health, Safety & Environment

Molybdoenzymes - general

Molybdenum Enzymes and How They Support Virulence in Pathogenic Bacteria

Mononuclear molybdoenzymes are highly versatile catalysts that occur in organisms in all domains of life, where they mediate essential cellular functions such as energy generation and detoxification reactions. Molybdoenzymes are particularly abundant in bacteria, where over 50 distinct types of enzymes have been identified to date. In bacterial pathogens, all aspects of molybdoenzyme biology such as molybdate uptake, cofactor biosynthesis, and function of the enzymes themselves, have been shown to affect fitness in the host as well as virulence. Although current studies are mostly focused on a few key pathogens such as Escherichia coli, Salmonella enterica, Campylobacter jejuni, and Mycobacterium tuberculosis, some common themes for the function and adaptation of the molybdoenzymes to pathogen environmental niches are emerging. Firstly, for many of these enzymes, their role is in supporting bacterial energy generation; and the corresponding pathogen fitness and virulence defects appear to arise from a suboptimally poised metabolic network. Secondly, all substrates converted by virulence-relevant bacterial Mo enzymes belong to classes known to be generated in the host either during inflammation or as part of the host signaling network, with some enzyme groups showing adaptation to the increased conversion of such substrates. Lastly, a specific adaptation to bacterial in-host survival is an emerging link between the regulation of molybdoenzyme expression in bacterial pathogens and the presence of immune system-generated reactive oxygen species. The prevalence of molybdoenzymes in key bacterial pathogens including ESKAPE pathogens, paired with the mounting evidence of their central roles in bacterial fitness during infection, suggest that they could be important future drug targets.

Q. F. Zhong, B. Kobe, and U. Kappler,Molybdenum Enzymes and How They Support Virulence in Pathogenic Bacteria, Frontiers in Microbiology, 2020, 11. https://doi.org/10.3389/fmicb.2020.615860

Functional mononuclear molybdenum enzymes: challenges and triumphs in molecular cloning, expression, and isolation

Mononuclear molybdenum enzymes catalyze a variety of reactions that are essential in the cycling of nitrogen, carbon, arsenic, and sulfur. For decades, the structure and function of these crucial enzymes have been investigated to develop a fundamental knowledge for this vast family of enzymes and the chemistries they carry out. Therefore, obtaining abundant quantities of active enzyme is necessary for exploring this family's biochemical capability. This mini-review summarizes the methods for overexpressing mononuclear molybdenum enzymes in the context of the challenges encountered in the process. Effective methods for molybdenum cofactor synthesis and incorporation, optimization of expression conditions, improving isolation of active vs. inactive enzyme, incorporation of additional prosthetic groups, and inclusion of redox enzyme maturation protein chaperones are discussed in relation to the current molybdenum enzyme literature. This article summarizes the heterologous and homologous expression studies providing underlying patterns and potential future directions.

B. Mintmier, S. Nassif, J. F. Stolz, and P. Basu,Functional mononuclear molybdenum enzymes: challenges and triumphs in molecular cloning, expression, and isolation, Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry, 2020, 25, 547-569.


The regulation of Moco biosynthesis and molybdoenzyme gene expression by moybdenum and iron in bacteria

Bacterial molybdoenzymes are key enzymes involved in the global sulphur, nitrogen and carbon cycles. These enzymes require the insertion of the moybdenum cofactor (Moco) into their active sites and are able to catalyse a large range of redox-reactions. Escherichia coli harbours nineteen different molybdoenzymes that require a tight regulation of their synthesis according to substrate availability, oxygen availability and the cellular concentration of moybdenum and iron. The synthesis and assembly of active molybdoenzymes are regulated at the level of transcription of the structural genes and of translation in addition to the genes involved in Moco biosynthesis. The action of global transcriptional regulators like FNR, NarXL/QP, Fur and ArcA and their roles on the expression of these genes is described in detail. In this review we focus on what is known about the moybdenum- and iron-dependent regulation of molybdoenzyme and Moco biosynthesis genes in the model organism E. coli. The gene regulation in E. coli is compared to two other well studied model organisms Rhodobacter capsulatus and Shewanella oneidensis.

A. Zupok, C. Iobbi-Nivol, V. Mejean, and S. Leimkuhler,The regulation of Moco biosynthesis and molybdoenzyme gene expression by moybdenum and iron in bacteria, Metallomics, 2019, 11, 1602-1624.


Mo enzymes Review           

Molybdenum   and tungsten enzymes redox properties - A brief overview

Metalloproteins and metal-containing enzymes are well known to be essential to life. Molybdenum   and tungsten are the heaviest transition metals used by biology. The mononuclear molybdenum   (and tungsten) containing enzymes have in common a particular conserved metal centre (Mo, W) coordinated by one or two pyranopterins. The metal coordination sphere is completed with oxygen and/or sulfur and/or selenium atoms in a diversity of arrangements. The enzymes organized in families (XO, SO and DMSOR) being diverse, can participate in a myriad of reactions involving atom insertion or abstraction and others, with different substrates and partners (physiological or not). The first and second coordination spheres tune the redox properties of the metal centres (and its catalytic features) for a wide range of reactions. In this review, a brief account is given on the main reactions catalysed by this class of enzymes, as well as a representative summary of the redox properties. (C) 2019 Elsevier B.V. All rights reserved.

C. M. Cordas, and J. J. G. Moura,Molybdenum   and tungsten enzymes redox properties - A brief overview, Coordination Chemistry Reviews, 2019, 394, 53-64.


Nitrite-dependent nitric oxide synthesis by molybdenum enzymes

Nitric oxide (NO) is an important gasotransmitter involved in numerous intra- and intercellular signaling events. In addition to the oxidative pathway of NO generation, which includes three NO synthase (NOS) isoforms in mammals, a reductive pathway contributes to NO generation. In this pathway, nitrite is reduced to NO by various metal-containing proteins. Among these, all members of the eukaryotic molybdenum (Mo)-dependent enzyme family were found to be able to reduce nitrite to NO. This Review focuses on the current state of research in the field of Mo-dependent nitrite reduction in eukaryotes. An overview on the five eukaryotic Mo-enzymes is given, and similarities as well as differences in their nitrite reduction mechanisms are presented and discussed in the context of physiological relevance.

D. Bender, and G. Schwarz,Nitrite-dependent nitric oxide synthesis by molybdenum enzymes, FEBS letters, 2018.


Molybdenum[nutrition review]

Molybdenum, a trace element essential for micro-organisms, plants, and animals, was discovered in 1778 by a Swedish chemist named Karl Scheele. Initially mistaken for lead, molybdenum was named after the Greek word molybdos, meaning lead-like. In the 1930s, it was recognized that ingestion of forage with high amounts of molybdenum by cattle caused a debilitating condition. In the 1950s, the essentiality of molybdenum was established with the discovery of the first molybdenum-containing enzymes. In humans, only 4 enzymes requiring molybdenum have been identified to date: sulfite oxidase, xanthine oxidase, aldehyde oxidase, and mitochondrial amidoxime-reducing component (mARC). Sulfite oxidase, an enzyme found in mitochondria, catalyzes oxidation of sulfite to sulfate, the final step in oxidation of sulfur amino acids (cysteine and methionine). Xanthine oxidase converts hypoxanthine to xanthine, and further converts xanthine to uric acid, preventing hypoxanthine, formed from spontaneous deamination of adenine, from leading to DNA mutations if paired with cytosine in place of thymine. Aldehyde oxidase is abundant in the liver and is an important enzyme in phase 1 drug metabolism. Finally, mARC, discovered less than a decade ago, works in concert with cytochrome b5 type B and NAD(H) cytochrome b5 reductase to reduce a variety of N-hydroxylated substrates, although the physiologic significance is still unclear. In the case of each of the molybdenum enzymes, activity is catalyzed via a tricyclic cofactor composed of a pterin, a dithiolene, and a pyran ring, called molybdenum cofactor (MoCo) (1).

J. A. Novotny, and C. A. Peterson,Molybdenum, Advances in nutrition, 2018, 9, 272-273.

Evolution of prokaryotic respiratory molybdoenzymes and the frequency of their genomic co-occurrence

Molybdoenzymes are an ancient protein family found in phylogenetically and ecologically diverse prokaryotes. Under anaerobic conditions, respiratory molybdoenzymes catalyze redox reactions that transfer electrons to a variety of substrates that act as terminal electron acceptors for energy generation. Here, we used probe sequences to conduct an extensive genomic survey and phylogenetic inference for NarG, DmsA, TorA and nine other respiratory molybdoenzyme subfamilies. Our analysis demonstrates their abundance in 60% of prokaryotic phyla. In contrast to many other autonomic genetic units in prokaryotes, the major route of evolution of their predominant subfamilies is vertical gene transfer, gene duplication and divergence. Our results show the robustness of genomic co-occurrence of respiratory molybdoenzymes genes, found in the majority of studied species, for most of the enzyme subfamilies. Genomes which encode for multiple respiratory molybdoenzymes are also enriched in genes regulating replication, recombination and mobility of genetic elements. Respiratory molybdoenzymes were found in prokaryotes associated with diverse environments occupying terrestrial, aquatic, food and host-related habitats, emphasizing their essential role in adaptation of prokaryotes to changing environments. Interestingly, host-associated prokaryotes such as human pathogens more frequently carry multiple respiratory molybdoenzyme genes compared with non-host-associated prokaryotes, highlighting the importance of metabolic flexibility in host-microbiome environments.

Harel, A., Haggblom, M. M., Falkowski, P. G., and Yee, N.,Evolution of prokaryotic respiratory molybdoenzymes and the frequency of their genomic co-occurrence, Fems Microbiology Ecology, 2016, 92.

Enzymatic characterization and gene identification of anconitate isomerase, an enzyme involved in assimilation of trans-aconitic acid, from Pseudomonas sp WU-0701

Trans-Aconitic acid is an unsaturated organic acid that is present in some plants such as soybean and wheat; however, it remains unclear how trans-aconitic acid is degraded and/or assimilated by living cells in nature.

From soil, we isolated Pseudomonas sp. WU-0701 assimilating trans-aconitic acid as a sole carbon source.

In the cell-free extract of Pseudomonas sp. WU-0701, aconitate isomerase (AI; EC activity was detected. Therefore, it seems likely that strain Pseudomonas sp. WU-0701 converts trans-aconitic acid to cis-aconitic acid with AI, and assimilates this via the tricarboxylic acid cycle.

For the characterization of AT from Pseudomonas sp. WU-0701, we performed purification, determination of enzymatic properties and gene identification of AI. The molecular mass of AT purified from cell-free extract was estimated to be similar to 25 kDa by both SDS/PAGE and gel filtration analyses, indicating that AT is a monomeric enzyme.

The optimal pH and temperature of purified AT for the reaction were 6.0 degrees C and 37 degrees C, respectively.

The gene ais encoding AT was cloned on the basis of the N-terminal amino acid sequence of the protein, and Southern blot analysis revealed that only one copy of ais is located on the bacterial genome. The gene ais contains an ORF of 786 bp, encoding a polypeptide of 262 amino acids, including the N-terminal 22 amino acids as a putative periplasm-targeting signal peptide. It is noteworthy that the amino acid sequence of AT shows 90% and 74% identity with molybdenum ABC transporter substrate-binding proteins of Pseudomonas psychrotolerans and Xanthomonas albilineans, respectively.

This is the first report on purification to homogeneity, characterization and gene identification of AI.

Yuhara, K., Yonehara, H., Hattori, T., Kobayashi, K., and Kirimura, K.,Enzymatic characterization and gene identification of aconitate isomerase, an enzyme involved in assimilation of trans-aconitic acid, from Pseudomonas sp WU-0701, Febs Journal, 2015, 282, 4257-4267.

Determining the role of molybdenum oxidases in drug metabolism

Jones, J. P.,Determining the role of molybdenum oxidases in drug metabolism, Drug Metabolism Reviews, 2015, 47, 9-9.

Bacterial molybdoenzymes: old enzymes for new purposes

Molybdoenzymes are widespread in eukaryotic and prokaryotic organisms where they play crucial functions in detoxification reactions in the metabolism of humans and bacteria, in nitrate assimilation in plants and in anaerobic respiration in bacteria. To be fully active, these enzymes require complex molybdenum-containing cofactors, which are inserted into the apoenzymes after folding. For almost all the bacterial molybdoenzymes, molybdenum cofactor insertion requires the involvement of specific chaperones. In this review, an overview on the molybdenum cofactor biosynthetic pathway is given together with the role of specific chaperones dedicated for molybdenum cofactor insertion and maturation. Many bacteria are involved in geochemical cycles on earth and therefore have an environmental impact. The roles of molybdoenzymes in bioremediation and for environmental applications are presented.

Leimkuhler, S., and Iobbi-Nivol, C.,Bacterial molybdoenzymes: old enzymes for new purposes, FEMS microbiology reviews, 2015.


Modeling of molybdoenzymes began even before the knowledge of the three-dimensional structure of these enzymes. The theoretical and experimental knowledge on these enzymes is vast and newer investigation is regularly pursued to understand the electronic aspect of these proteins using computational means. The present review deals with some unique observation regarding the structure, function and reactivity of some models and native proteins in rationalizing the choice of diverse substrates in seemingly similar enzymes such as Nap (nitrate reductase) and Fdh (formate dehydrogenase) and the dual form of a specific substrate of an enzyme like trimethylamine N-oxide reductase (TAMOR) and providing the electronic reason for the inhibition in the oxypurinol-inhibited xanthine oxidase (XO)

Cerqueira, N. M. F. S., Pakhira, B., and Sarkar, S., Theoretical studies on mechanisms of some Mo enzymes, Journal of Biological Inorganic Chemistry, 2015, 20, 323-335.

Conformational selection underlies recognition of a molybdoenzyme by its dedicated chaperone

Molecular recognition is central to all biological processes. Understanding the key role played by dedicated chaperones in metalloprotein folding and assembly requires the knowledge of their conformational ensembles. In this study, the NarJ chaperone dedicated to the assembly of the membrane-bound respiratory nitrate reductase complex NarGHI, a molybdenum-iron containing metalloprotein, was taken as a model of dedicated chaperone. The combination of two techniques ie site-directed spin labeling followed by EPR spectroscopy and ion mobility mass spectrometry, was used to get information about the structure and conformational dynamics of the NarJ chaperone upon binding the N-terminus of the NarG metalloprotein partner.

By the study of singly spin-labeled proteins, the E119 residue present in a conserved elongated hydrophobic groove of NarJ was shown to be part of the interaction site.

Moreover, doubly spin-labeled proteins studied by pulsed double electron-electron resonance (DEER) spectroscopy revealed a large and composite distribution of inter-label distances that evolves into a single preexisting one upon complex formation.

Additionally, ion mobility mass spectrometry experiments fully support these findings by revealing the existence of several conformers in equilibrium through the distinction of different drift time curves and the selection of one of them upon complex formation.

Taken together our work provides a detailed view of the structural flexibility of a dedicated chaperone and suggests that the exquisite recognition and binding of the N-terminus of the metalloprotein is governed by a conformational selection mechanism.

Lorenzi, Magali, Sylvi, Lea, Gerbaud, Guillaume, Mileo, Elisabetta, Halgand, Frederic, Walburger, Anne, Vezin, Herve, Belle, Valerie, Guigliarelli, Bruno, and Magalon, Axel, Conformational selection underlies recognition of a molybdoenzyme by its dedicated chaperone, PloS one, 2012, 7, e49523.

A volume in the series Metal Ions in Biological Systems is devoted to molybdenum and tungsten:

A. Sigel and H. Sigel (eds.), Metal Ions in Biological Systems, Vol. 39: Molybdenum and Tungsten: Their Roles in Biological Processes, Marcel Dekker, New York, 2002.

See especially:

Stiefel, E.L., The biogeochemistry of molybdenum and tungsten, Molybdenum and Tungsten: Their Roles in Biological Processes, 2002, 39, 1-29.
Lowe, D.J., Enzymes of the xanthine oxidase family: The role of molybdenum, Molybdenum and Tungsten: Their Roles in Biological Processes, 2002, 39, 455-479.
Turnlund, J.R., Molybdenum metasuklbolism and requirements in humans, Molybdenum and Tungsten: Their Roles in Biological Processes, 2002, 39, 727-739.
Lagarde, F. and Leroy, M., Metabolism and toxicity of tungsten in humans and animals, Molybdenum and Tungsten: Their Roles in Biological Processes , 2002, 39, 741-759.
Schindelin, H., Kisker, C., Rees , D.C. , The molybdenum-cofactor: a crystallographic perspective, Journal Of Biological Inorganic Chemistry , 1997, 2 , 773-781.
Mendel, R.R., The role of the molybdenum cofactor in humans, Biofactors, 2000, 11 , 147-148.
Vorholt, J.A. and Thauer, R. K., Molybdenum and tungsten enzymes in C1 metabolism, Molybdenum and Tungsten: Their Roles in Biological Processes, 2002, 39, 571-619.
L'vov, N.P., Nosikov, A. N., and Antipov, A. N., Tungsten-containing enzymes, Biochemistry-Moscow, 2002, 67, 196-200.
Noodleman, L., Lovell, T., Liu, T. Q., Himo, F., and Torres, R. A., Insights into properties and energetics of iron-sulfur proteins from simple clusters to nitrogenase, Current Opinion in Chemical Biology , 2002, 6, 259-273.
Williams, R.J.P. and da Silva, J. J. R. F., The involvement of molybdenum in life, Biochemical and Biophysical Research Communications, 2002, 292, 293-299.
Hille, R., Molybdenum and tungsten in biology, Trends in Biochemical Sciences , 2002, 27, 360-367.

Molybdenum-containing hydroxylases catalyze the hydroxylation of carbon centers using oxygen derived ultimately from water, rather than O2, as the source of the oxygen atom incorporated into the product, and do not require an external source of reducing equivalents. The mechanism by which this interesting chemistry takes place has been the subject of investigation for some time, and in the last several years the chemical course of the reaction has become increasingly well understood. This review summarizes recent mechanistic and structure/function studies of the molybdenum-containing hydroxylases.

Hille, R., Molybdenum-containing hydroxylases, Archives of Biochemistry and Biophysics, 2005, 433, 107-116.

Review of molybdenum uptake into the cell, via formation of the molybdenum cofactor and its storage, to the final modification of molybdenum cofactor and its insertion into apo-metalloenzymes

Mendel, R.R., Molybdenum: biological activity and metabolism, Dalton Transactions, 2005, 3404-3409.
Schwarz, G., Molybdenum cofactor biosynthesis and deficiency, Cellular and Molecular Life Sciences, 2005, 62, 2792-2810.
Noriega, C., Hassett, D. J., and Rowe, J. J., The mobA gene is required for assimilatory and respiratory nitrate reduction but not xanthine dehydrogenase activity in Pseudomonas aeruginosa, Current Microbiology, 2005, 51, 419-424.

Molybdenum is essential for most biological systems as it is required by enzymes catalyzing reactions in carbon, sulfur and nitrogen metabolism. Molybdenum is biologically inactive unless it is complexed by a cofactor. Mo is bound to a pterin forming the molybdenum cofactor (Moco) which is the active compound at the catalytic site of Mo-enzymes except nitrogenase. In eukaryotes, the most prominent Mo-enzymes are (1) sulfite oxidase, which catalyzes the final step in the degradation of sulfur-containing amino acids and is involved in detoxifying excess sulfite, (2) xanthine dehydrogenase, which is involved in purine catabolism and reactive oxygen production, (3) aldehyde oxidase, which oxidizes a variety of aldehydes and is essential for the biosynthesis of the phytohormone abscisic acid, and in autotrophic organisms and (4) nitrate reductase, which catalyzes the key step in inorganic nitrogen assimilation. Mo-enzymes, except plant sulfite oxidase, need at least one more redox active center, many of them involving iron in electron transfer. The biosynthesis of Moco involves the complex interaction of six proteins and is a process of four steps, which also includes iron as well as copper in an indespensable way. Moco as released after synthesis is likely to be distributed to the apoproteins of Mo-enzymes by putative Moco-carrier proteins. Xanthine dehydrogenase and aldehyde oxidase, but not sulfite oxidase and nitrate reductase, require the postranslational sulfuration of their Mo-site for becoming active. This final maturation step is catalyzed by a Moco-sulfurase enzyme, which mobilizes sulfur from L-cysteine in a pyridoxal phosphate-dependent manner as typical for cysteine desulfurases.

Mendel, R. R. and Bittner, F., Cell biology of molybdenum, Biochimica et Biophysica Acta-Molecular Cell Research, 2006, 1763, 621-635.

Review of molybdenum uptake into the cell, via formation of the molybdenum cofactor and its storage, to the final modification of molybdenum cofactor and its insertion into apo-metalloenzymes

Mendel, R.R., Molybdenum: biological activity and metabolism, Dalton Transactions, 2005, 3404-3409.
Schwarz, G. and Mendel, R. R., Molybdenum cofactor biosynthesis and molybdenum enzymes, Annual Review of Plant Biology, 2006, 57, 623-647
Harrison, R., Milk xanthine oxidase: Properties and physiological roles, International Dairy Journal, 2006, 16, 546-554.

An issue of Journal Inorganic Biochemistry dedicated to Dr Ed Stiefel is devoted largely to molybdenum biology and enzymes:


Preface for Stiefel Issue1543
John H Dawson and Harry B Gray
Edward I Stiefel – Catalysis by Enthusiasm1544
Jay Groves and Tom Spiro
Edward I Stiefel – A Personal Retrospective1546
Stephen J Lippard
Personal Remembrance
Ferrocentric memories of Edward I Stiefel1548
Elizabeth C Theil
General Review
Life, the environment and our ecosystem1550
R J P Williams
The chemistry and biochemistry of molybdenum

Facets of early transition metal–sulfur chemistry: Metal–sulfur ligand redox, induced internal electron transfer, and the reactions of metal–sulfur complexes with alkynes 1562

Charles G Young
Reactivity of potential anti-diabetic molybdenum(VI) complexes in biological media: A XANES spectroscopic study1586
Aviva Levina, Andrew IMcLeod, Jan Seuring and Peter ALay
Sulfur K-edge XAS of WV@O vs MoV@O bis(dithiolene) complexes: Contributions of relativistic effects to electronic structure and reactivity of tungsten enzymes1594
Adam L Tenderholt, Robert K Szilagyi, Richard H Holm, Keith O Hodgson, Britt Hedman and Edward I Solomon
Synthesis, characterization, and spectroscopy of model molybdopterin complexes 601
Sharon J Nieter Burgmayer, Mary Kim, Rebecca Petit, Amy Rothkopf, Alison Kim, Shadia BelHamdounia, Ying Hou,
Arpad Somogyi, Diana Habel-Rodriguez, Antonio Williams and Martin L Kirk
EPR characterization of the molybdenum(V) forms of formate dehydrogenase from Desulfovibrio desulfuricans ATCC 27774 upon formate reduction1617
Marý´a G Rivas, Pablo J Gonza´lez, Carlos D Brondino, Jose´ J G Moura and Isabel Moura

Toward modeling the high chloride, low pH form of sulfite oxidase: Ka-band ESEEM of equatorial chloro ligands in oxomolybdenum(V) complexes1623

Andrei V Astashkin, Eric L Klein and John H Enemark
Molecular insights into nitrogenase FeMoco insertion – The role of His 274 and His 451 of MoFe protein a subunit 1630
Aaron W Fay, Yilin Hu, Benedikt Schmid and Markus W Ribbe
Alkyne substrate interaction within the nitrogenase MoFe protein1642
Patricia C Dos Santos, Suzanne M Mayer, Brett M Barney, Lance C Seefeldt and Dennis R Dean
Conformations generated during turnover of the Azotobacter vinelandii nitrogenase MoFe protein and their relationship to physiological function1649
Karl Fisher, David J Lowe, Pedro Tavares, Alice S Pereira, Boi Hanh Huynh, Dale Edmondson and William E Newton

Model molybdopterin complexes

New model pterin-substituted dithiolene complexes of molybdenum(V) and molybdenum(IV) for the molybdenum cofactor are reported: Tp*MoX(pterin-R-dithiolene) (Tp* = tris(3,5,-dimethylpyrazolyl)borate), X = O, S, R = aryl.

Burgmayer, S. J. N., Kim, M., Petit, R., Rothkopf, A., Kim, A., BelHamdounia, S., Hou, Y., Somogyi, A., Habel-Rodriguez, D., Williams, A., and Kirk, M. L., Synthesis, characterization, and spectroscopy of model molybdopterin complexes, Journal of Inorganic Biochemistry, 2007, 101, 1601-1616.

Active sites of molybdoenzymes

Molybdenum enzymes can be grouped on the basis of the structure of the metal centre:

Active sites of molybdoenzymes
molybdenum hydroxylases (pyranopterin)MoOS(OH) Xanthine oxidase and xanthine dehydrogenase
eukaryotic oxotransferases (pyranopterin)MoO2(S- Cys) sulfite oxidases and plant nitrate reductases.
bacterial oxotransferases (pyranopterin)2MoOX pyranopterin, cofactor; X, ligated serine, cysteine or selenocysteine

The active sites possess a catalytically labile Mo-OH (or possibly Mo-OH 2) group that is transferred to substrate in the course of the hydroxylation reaction. Water rather than molecular oxygen is the ultimate source of the oxygen atom incorporated into product.

Hille, R., Molybdenum enzymes, Essays Biochem., 1999, 34, 125-137.

Review: active centres

Recent characterisation of molybdenum and tungsten enzymes revealed novel structural types of reaction centres, as well as providing new subjects of interest as synthetic chemical analogues. This tutorial review highlights the structure/reactivity relationships of the enzyme reaction centres and chemical analogues. Chemical analogues for the oxygen atom transfer enzymes have been well expanded in structure and reactivity. Other types of chemical analogues that exhibit different coordination chemistry have recently been presented for reaction centres of the hydroxylation and dehydrogenation enzymes and others

Sugimoto, H. and Tsukube, H., Chemical analogues relevant to molybdenum and tungsten enzyme reaction centres toward structural dynamics and reaction diversity, Chemical Society Reviews, 2008, 37, 2609-2619.

Review: molybdenum and tungsten enzymes

Tungsten is widely distributed in biology; the majority of the tungsten-containing enzymes so far purified are from anaerobic archaea and bacteria. Tungsten is taken up by cells as tungstate, and then coordinated by sulfur in a cofactor, tungstopterin. equivalent to molybdopterin, the active center in several molybdenum-containing enzymes.

In biology tungsten is different from molybdenum. This review describes the (bio)molecular basis of this differential cellular use of W to Mo in terms of their active transport, cofactor synthesis, and functioning as catalytically active sites.

Bevers, L. E., Hagedoorn, P. L., and Hagen, W. R., The bioinorganic chemistry of tungsten, Coordination Chemistry Reviews, 2009, 253, 269-290

Cell biology in plants and animals: review

The transition element molybdenum needs to be complexed by a special cofactor in order to gain catalytic activity. With the exception of bacterial molybdenum nitrogenase, where molybdenum is a constituent of the FeMo-cofactor, molybdenum is bound to a pterin, thus forming the molybdenum cofactor Moco, which in different variants is the active compound at the catalytic site of all other molybdenum containing enzymes. In eukaryotes, the most prominent Mo-enzymes are nitrate reductase, sulfite oxidase, xanthine dehydrogenase, aldehyde oxidase, and the mitochondrial amidoxime reductase. The biosynthesis of Moco involves the complex interaction of six proteins and is a process of four steps, which also requires iron, ATP and copper. After its synthesis, Moco is distributed to the apoproteins of molybdenum -enzymes by Moco-carrier/binding proteins. A deficiency in the biosynthesis of Moco has lethal consequences for the respective organisms. In humans, Moco deficiency is a severe inherited inborn error in metabolism resulting in severe neurodegeneration in newborns and causing early childhood death. This article is part of a Special Issue entitled: Cell Biology of Metals. (C) 2012 Elsevier BM. All rights reserved

Mendel, Ralf R. and Kruse, Tobias, Cell biology of molybdenum in plants and humans, Biochimica et Biophysica Acta-Molecular Cell Research, 2012, 1823, 1568-1579

Molybdenum Cofactor Deficiency Mimics Cerebral Palsy: Differentiating Factors for Diagnosis

We describe an infant with molybdenum cofactor deficiency, initially diagnosed as cerebral palsy. Clinical features of molybdenum cofactor deficiency, e.g., neonatal seizures, hypertonus/hypotonus, and feeding and respiratory difficulties, resemble those of neonatal hypoxic-ischemic encephalopathy. Our patient, a 2-year-old boy, presented with spastic quadriplegia and mental retardation. He manifested intractable neonatal seizures and diffuse cerebral atrophy. When admitted with bronchitis at age 18 months, his uric acid levels in blood and urine were undetectable. A urinary sulfite test revealed positive results. Further tests revealed elevated urinary levels of xanthine, hypoxanthine, and S-sulfocystein. Sequencing of the MOCS2A gene revealed heterozygosity for c.[265T>C] + [266A>G], diagnosed as molybdenum cofactor deficiency type B. Neonatal seizures, progressive cerebral atrophy, and low serum levels of uric acid may provide diagnostic clues in patients with cerebral palsy of undetermined cause. (C) 2012 Elsevier Inc. All rights reserved

Kikuchi, Kenjiro, Hamano, Shin ichiro, Mochizuki, Hiroshi, Ichida, Kimiyoshi, and Ida, Hiroyuki, Molybdenum Cofactor Deficiency Mimics Cerebral Palsy: Differentiating Factors for Diagnosis, Pediatric Neurology, 2012, 47, 147-149.

X-ray absorption spectra of molybdoenzymes

The X-ray absorption spectra at the molybdenum and selenium K- edges and the tungsten L-2,L-3-edges are reported for fourteen Mo(IV) and W(IV,VI) bis(dithiolene) complexes related to the active sites of molybdo- and tungstoenzymes. These and previous XAS results should prove useful in characterizing and refining metric features and structures of enzyme sites.

Musgrave, K.B., Lim, B. S., Sung, K. M., Holm, R. H., Hedman, B., and Hodgson, K. O., X-ray spectroscopy of enzyme active site analogues and related molecules: Bis(dithiolene)molybdenum(IV) and -tungsten(IV,VI) complexes with variant terminal ligands, Inorganic Chemistry, 2000, 39 , 5238-5247.

Structural and functional models in molybdenum and tungsten bioinorganic chemistry: description of selected model complexes, present scenario and possible future scopes

A brief description about some selected model complexes in molybdenum and tungsten bioinorganic chemistry is provided. The synthetic strategies involved and their limitations are discussed. Current status of molybdenum and tungsten bioinorganic modeling chemistry is presented briefly and synthetic problems associated therein are analyzed. Possible future directions which may expand the scope of modeling chemistry are suggested.

Majumdar, A., Structural and functional models in molybdenum and tungsten bioinorganic chemistry: description of selected model complexes, present scenario and possible future scopes, Dalton Transactions, 2014, 43, 8990-9003.

Users of the Database should be aware that inclusion of an abstract in the Database does not imply any IMOA endorsement of the accuracy or reliability of the reported data or the quality of a publication.