TY - JOUR A1 - Yokoyama, Kenichi A1 - Leimkühler, Silke T1 - The role of FeS clusters for molybdenum cofactor biosynthesis and molybdoenzymes in bacteria JF - Biochimica et biophysica acta : Molecular cell research N2 - The biosynthesis of the molybdenum cofactor (Moco) has been intensively studied, in addition to its insertion into molybdoenzymes. In particular, a link between the assembly of molybdoenzymes and the biosynthesis of FeS clusters has been identified in the recent years: 1) the synthesis of the first intermediate in Moco biosynthesis requires an FeS-cluster containing protein, 2) the sulfurtransferase for the dithiolene group in Moco is also involved in the synthesis of FeS clusters, thiamin and thiolated tRNAs, 3) the addition of a sulfido-ligand to the molybdenum atom in the active site additionally involves a sulfurtransferase, and 4) most molybdoenzymes in bacteria require FeS clusters as redox active cofactors. In this review we will focus on the biosynthesis of the molybdenum cofactor in bacteria, its modification and insertion into molybdoenzymes, with an emphasis to its link to FeS cluster biosynthesis and sulfur transfer. (C) 2014 Elsevier B.V. All rights reserved. KW - Molybdenum-iron-iron-sulfur cluster KW - Molybdenum cofactor KW - tRNA KW - Sulfur transfer KW - L-Cysteine desulfurase Y1 - 2015 U6 - https://doi.org/10.1016/j.bbamcr.2014.09.021 SN - 0167-4889 SN - 0006-3002 VL - 1853 IS - 6 SP - 1335 EP - 1349 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Hartmann, Tobias A1 - Schwanhold, Nadine A1 - Leimkühler, Silke T1 - Assembly and catalysis of molybdenum or tungsten-containing formate dehydrogenases from bacteria JF - Biochimica et biophysica acta : Proteins and proteomics N2 - The global carbon cycle depends on the biological transformations of C-1 compounds, which include the reductive incorporation of CO2 into organic molecules (e.g. in photosynthesis and other autotrophic pathways), in addition to the production of CO2 from formate, a reaction that is catalyzed by formate dehydrogenases (FDHs). FDHs catalyze, in general, the oxidation of formate to CO2 and H+. However, selected enzymes were identified to act as CO2 reductases, which are able to reduce CO2 to formate under physiological conditions. This reaction is of interest for the generation of formate as a convenient storage form of H-2 for future applications. Cofactor-containing FDHs are found in anaerobic bacteria and archaea, in addition to facultative anaerobic or aerobic bacteria. These enzymes are highly diverse and employ different cofactors such as the molybdenum cofactor (Moco), FeS clusters and flavins, or cytochromes. Some enzymes include tungsten (W) in place of molybdenum (Mo) at the active site. For catalytic activity, a selenocysteine (SeCys) or cysteine (Cys) ligand at the Mo atom in the active site is essential for the reaction. This review will focus on the characterization of Mo- and W-containing FDHs from bacteria, their active site structure, subunit compositions and its proposed catalytic mechanism. We will give an overview on the different mechanisms of substrate conversion available so far, in addition to providing an outlook on bio-applications of FDHs. This article is part of a Special Issue entitled: Cofactor-dependent proteins: evolution, chemical diversity and bio-applications. (C) 2014 Elsevier B.V. All rights reserved. KW - Molybdenum cofactor KW - L-Cysteine desulfurase KW - Formate dehydrogenase KW - Chaperone KW - Bis-MGD Y1 - 2015 U6 - https://doi.org/10.1016/j.bbapap.2014.12.006 SN - 1570-9639 SN - 0006-3002 VL - 1854 IS - 9 SP - 1090 EP - 1100 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Mendel, Ralf R. A1 - Leimkühler, Silke T1 - The biosynthesis of the molybdenum cofactors JF - Journal of biological inorganic chemistry N2 - The biosynthesis of the molybdenum cofactors (Moco) is an ancient, ubiquitous, and highly conserved pathway leading to the biochemical activation of molybdenum. Moco is the essential component of a group of redox enzymes, which are diverse in terms of their phylogenetic distribution and their architectures, both at the overall level and in their catalytic geometry. A wide variety of transformations are catalyzed by these enzymes at carbon, sulfur and nitrogen atoms, which include the transfer of an oxo group or two electrons to or from the substrate. More than 50 molybdoenzymes were identified to date. In all molybdoenzymes except nitrogenase, molybdenum is coordinated to a dithiolene group on the 6-alkyl side chain of a pterin called molybdopterin (MPT). The biosynthesis of Moco can be divided into three general steps, with a fourth one present only in bacteria and archaea: (1) formation of the cyclic pyranopterin monophosphate, (2) formation of MPT, (3) insertion of molybdenum into molybdopterin to form Moco, and (4) additional modification of Moco in bacteria with the attachment of a nucleotide to the phosphate group of MPT, forming the dinucleotide variant of Moco. This review will focus on the biosynthesis of Moco in bacteria, humans and plants. KW - Molybdenum KW - Molybdenum cofactor KW - cPMP KW - bis-MGD KW - Sulfuration KW - Sulfite oxidase Y1 - 2015 U6 - https://doi.org/10.1007/s00775-014-1173-y SN - 0949-8257 SN - 1432-1327 VL - 20 IS - 2 SP - 337 EP - 347 PB - Springer CY - New York ER - TY - JOUR A1 - Boehmer, Nadine A1 - Hartmann, Tobias A1 - Leimkühler, Silke T1 - The chaperone FdsC for Rhodobacter capsulatus formate dehydrogenase binds the bis-molybdopterin guanine dinucleotide cofactor JF - FEBS letters : the journal for rapid publication of short reports in molecular biosciences N2 - Molybdoenzymes are complex enzymes in which the molybdenum cofactor (Moco) is deeply buried in the enzyme. Most molybdoenzymes contain a specific chaperone for the insertion of Moco. For the formate dehydrogenase FdsGBA from Rhodobacter capsulatus the two chaperones FdsC and FdsD were identified to be essential for enzyme activity, but are not a subunit of the mature enzyme. Here, we purified and characterized the FdsC protein after heterologous expression in Escherichia coli. We were able to copurify FdsC with the bound Moco derivate bis-molybdopterin guanine dinucleotide. This cofactor successfully was used as a source to reconstitute the activity of molybdoenzymes. Structured summary of protein interactions: FdsC and FdsC bind by molecular sieving (View interaction) FdsD binds to RcMobA by surface plasmon resonance (View interaction) FdsC binds to RcMobA by surface plasmon resonance (View interaction) FdsC binds to FdsA by surface plasmon resonance (View interaction) KW - Molybdenum cofactor KW - L-cysteine desulfurase KW - Formate dehydrogenase KW - Chaperone KW - bis-MGD Y1 - 2014 U6 - https://doi.org/10.1016/j.febslet.2013.12.033 SN - 0014-5793 SN - 1873-3468 VL - 588 IS - 4 SP - 531 EP - 537 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Iobbi-Nivol, Chantal A1 - Leimkühler, Silke T1 - Molybdenum enzymes, their maturation and molybdenum cofactor biosynthesis in Escherichia coli JF - Biochimica et biophysica acta : Bioenergetics N2 - Molybdenum cofactor (Moco) biosynthesis is an ancient, ubiquitous, and highly conserved pathway leading to the biochemical activation of molybdenum. Moco is the essential component of a group of redox enzymes, which are diverse in terms of their phylogenetic distribution and their architectures, both at the overall level and in their catalytic geometry. A wide variety of transformations are catalyzed by these enzymes at carbon, sulfur and nitrogen atoms, which include the transfer of an oxo group or two electrons to or from the substrate. More than 50 molybdoenzymes were identified in bacteria to date. In molybdoenzymes Mo is coordinated to a dithiolene group on the 6-alkyl side chain of a pterin called molybdopterin (MPT). The biosynthesis of Moco can be divided into four general steps in bacteria: I) formation of the cyclic pyranopterin monophosphate, 2) formation of MPT, 3) insertion of molybdenum into molybdopterin to form Moco, and 4) additional modification of Moco with the attachment of GMP or CMP to the phosphate group of MPT, forming the dinucleotide variant of Moco. This review will focus on molybdoenzymes, the biosynthesis of Moco, and its incorporation into specific target proteins focusing on Escherichia coli. This article is part of a Special Issue entitled: Metals in Bioenergetics and Biomimetics Systems. KW - Molybdenum cofactor KW - Molybdenum KW - Dithiolene KW - Molybdopterin KW - Bis-MGD KW - Moco Y1 - 2013 U6 - https://doi.org/10.1016/j.bbabio.2012.11.007 SN - 0005-2728 VL - 1827 IS - 8-9 SP - 1086 EP - 1101 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Badalyan, Artavazd A1 - Neumann-Schaal, Meina A1 - Leimkühler, Silke A1 - Wollenberger, Ursula T1 - A Biosensor for aromatic aldehydes comprising the mediator dependent PaoABC-Aldehyde oxidoreductase JF - Electroanalysis : an international journal devoted to fundamental and practical aspects of electroanalysis N2 - A novel aldehyde oxidoreductase (PaoABC) from Escherichia coli was utilized for the development of an oxygen insensitive biosensor for benzaldehyde. The enzyme was immobilized in polyvinyl alcohol and currents were measured for aldehyde oxidation with different one and two electron mediators with the highest sensitivity for benzaldehyde in the presence of hexacyanoferrate(III). The benzaldehyde biosensor was optimized with respect to mediator concentration, enzyme loading and pH using potassium hexacyanoferrate(III). The linear measuring range is between 0.5200 mu M benzaldehyde. In correspondence with the substrate selectivity of the enzyme in solution the biosensor revealed a preference for aromatic aldehydes and less effective conversion of aliphatic aldehydes. The biosensor is oxygen independent, which is a particularly attractive feature for application. The biosensor can be applied to detect contaminations with benzaldehyde in solvents such as benzyl alcohol, where traces of benzaldehyde in benzyl alcohol down to 0.0042?% can be detected. KW - Aldehyde oxidoreductase KW - Benzaldehyde KW - Biosensor KW - Aromatic aldehydes KW - Molybdenum cofactor Y1 - 2013 U6 - https://doi.org/10.1002/elan.201200362 SN - 1040-0397 VL - 25 IS - 1 SP - 101 EP - 108 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Leimkühler, Silke A1 - Wuebbens, Margot M. A1 - Rajagopalan, K. V. T1 - The history of the discovery of the molybdenum cofactor and novel aspects of its biosynthesis in bacteria JF - Coordination chemistry reviews N2 - The biosynthesis of the molybdenum cofactor in bacteria is described with a detailed analysis of each individual reaction leading to the formation of stable intermediates during the synthesis of molybdopterin from GTP. As a starting point, the discovery of molybdopterin and the elucidation of its structure through the study of stable degradation products are described. Subsequent to molybdopterin synthesis, the molybdenum atom is added to the molybdopterin dithiolene group to form the molybdenum cofactor. This cofactor is either inserted directly into specific molybdoenzymes or is further modified by the addition of nucleotides to molybdopterin phosphate group or the replacement of ligands at the molybdenum center. KW - Molybdenum cofactor KW - Molybdopterin KW - Precursor Z KW - Molybdopterin guanine dinucleotide cofactor KW - Urothione KW - Dithiolene group Y1 - 2011 U6 - https://doi.org/10.1016/j.ccr.2010.12.003 SN - 0010-8545 VL - 255 IS - 9-10 SP - 1129 EP - 1144 PB - Elsevier CY - Lausanne ER -