Molybdenum enzymes in higher organisms

Background: Localization and identification of interaction partners of two splice variants of the human 3-mercaptopyruvate sulfurtransferase TUM1. Results: We show that TUM1 interacts with proteins involved in Moco and FeS cluster biosynthesis. Conclusion: Human TUM1 is a dual localized protein in the cytosol and mitochondria with distinct roles in sulfur transfer and interaction partners. Significance: The study contributes to the sulfur transfer pathway for the biosynthesis of sulfur-containing biofactors.

Section: Glnmentioning

confidence: 95%

Characterization and Interaction Studies of Two Isoforms of the Dual Localized 3-Mercaptopyruvate Sulfurtransferase TUM1 from Humans

Fräsdorf

Radon

Leimkühler

2014

“…Molybdenum enzymes generally catalyze the transfer of an oxygen atom (ultimately derived from or incorporated into water) to or from a substrate (5). Each reaction, either reduction or oxidation, involves the transfer of two electrons, thereby causing a change in the oxidation state of the molybdenum atom in the substratebinding site from IV to VI or vice versa.…”

Section: What Is the Molybdenum Cofactor?mentioning

confidence: 99%

“…More than 50 enzymes are known to be molybdenumdependent. The vast majority of them are found in bacteria, whereas only seven have been identified in eukaryotes (4,5). It is somewhat surprising that not all organisms need molybdenum.…”

mentioning

confidence: 99%

The Molybdenum Cofactor

Mendel

2013

244

181

The transition element molybdenum needs to be complexed by a special cofactor to gain catalytic activity. Molybdenum is bound to a unique pterin, thus forming the molybdenum cofactor (Moco), which, in different variants, is the active compound at the catalytic site of all molybdenum-containing enzymes in nature, except bacterial molybdenum nitrogenase. The biosynthesis of Moco involves the complex interaction of six proteins and is a process of four steps, which also require iron, ATP, and copper. After its synthesis, Moco is distributed, involving Mocobinding proteins. A deficiency in the biosynthesis of Moco has lethal consequences for the respective organisms.The transition element molybdenum is an essential micronutrient for microorganisms, plants, and animals (1). Surprisingly, molybdenum itself is catalytically inactive in biological systems until it is complexed by a special scaffold (2). One type of scaffold is the ubiquitous pterin-based molybdenum cofactor (Moco), 2 which, in different variants, forms part of the active centers of all molybdenum enzymes in living organisms, except one. This exception is bacterial nitrogenase, which harbors the other type of cofactor, namely the Fe-S cluster-based FeMo cofactor, which is found only once in nature (for details, compare the minireview of Hu and Ribbe (62) in this thematic series). Molybdenum belongs to the group of trace elements, i.e. the organism needs it only in minute amounts; however, unavailability of molybdenum is lethal for the organism. Molybdenum is very abundant in the oceans in the form of the molybdate anion (3). In soils, the molybdate anion is the only form of molybdenum that is available for bacteria, plants, and fungi. More than 50 enzymes are known to be molybdenumdependent. The vast majority of them are found in bacteria, whereas only seven have been identified in eukaryotes (4, 5). It is somewhat surprising that not all organisms need molybdenum. The commonly used eukaryotic model organism yeast plays no role in molybdenum research, as Saccharomyces cerevisiae does not contain either molybdenum enzymes or the Moco biosynthesis pathway. Also Schizosaccharomyces pombe does not use molybdenum, whereas Pichia pastoris needs molybdenum. Genome-wide database analyses revealed a significant number of bacteria and unicellular eukaryotes that do not need molybdenum, whereas all multicellular eukaryotes are dependent on molybdenum (6). In addition, mainly anaerobic archaea and some bacteria are molybdenum-independent, but they require tungsten for their growth (7). In the periodic table of elements, tungsten lies directly below molybdenum and features chemical properties similar to molybdenum.Molybdenum metabolism is tightly connected to Fe-S cluster synthesis in that some of the molybdenum enzymes and Moco biosynthesis itself depend on Fe-S enzymes and on a mitochondrial transporter that is known to be crucial for the maturation of cytosolic Fe-S proteins. Moreover, Moco biosynthesis recruits mechanisms previously known from Fe-S cluster synthe...

“…For Moco biosynthesis in humans, the E1-like protein MOCS3 forms a thiocarboxylate group at the C-terminal glycine of the ␤-grasp fold protein MOCS2A (4 -6). Moco is required for the activity of xanthine dehydrogenase, aldehyde oxidase, sulfite oxidase, and the mitochondrial amidoxime reducing components, hmARC1 and hmARC2, in humans (7). In Moco, two sulfur atoms of the molybdopterin (MPT) moiety coordinate the molybdenum atom in the final structure (8).…”

mentioning

confidence: 99%

Dual Role of the Molybdenum Cofactor Biosynthesis Protein MOCS3 in tRNA Thiolation and Molybdenum Cofactor Biosynthesis in Humans

Chowdhury

Dosche

Löhmannsröben

et al. 2012

Background: E1-like proteins are required for activation and thiocarboxylation of ␤-grasp fold proteins involved in sulfur transfer to cofactors and tRNA. Results: MOCS3 interacts with both URM1 and MOCS2A in vivo and in vitro. Conclusion: Molybdenum cofactor biosynthesis and tRNA thiolation steps are linked by the MOCS3 protein in humans. Significance: The studies contribute to understanding the mechanism of protein conjugation and thiocarboxylate formation in sulfur transfer pathways.