Article
Cell Biology
Aileen K. Sewell, Min Han
Summary: Molybdenum cofactor is essential for human development and supplementation of Moco has been explored as a therapy for Moco-deficient patients. Research using C. elegans suggests that protein-bound Moco supplementation could have significant clinical implications for treating molybdenum cofactor deficiency.
GENES & DEVELOPMENT
(2021)
Review
Biochemistry & Molecular Biology
Ralf R. Mendel, Guenter Schwarz
Summary: This review summarizes the research history and importance of sulfite oxidase, a molybdenum-containing enzyme that plays a crucial role in redox regulation, signaling, and metabolism in both plants and animals.
Article
Cell Biology
Kurt Warnhoff, Thomas W. Hercher, Ralf R. Mendel, Gary Ruvkun
Summary: Protein-bound Moco is a stable and bioavailable form of Moco taken up by C. elegans from its diet, serving as a successful dietary supplement in rescuing a C. elegans model of Moco deficiency. This finding suggests a potential new strategy for producing and delivering therapeutically active Moco to treat human Moco deficiency.
GENES & DEVELOPMENT
(2021)
Article
Genetics & Heredity
Anna-Theresa Mellis, Juliane Roeper, Albert L. Misko, Joshua Kohl, Guenter Schwarz
Summary: Molybdenum cofactor deficiency (MoCD) is a metabolic genetic disorder characterized by the loss of sulfite oxidase (SO) function, leading to the accumulation of sulfurous compounds. Mitochondria are severely affected in MoCD, showing altered function and morphology which contribute to the disease phenotype.
FRONTIERS IN GENETICS
(2021)
Article
Endocrinology & Metabolism
Alexander Tobias Kaczmarek, Daniel Bender, Titus Gehling, Joshua Benedict Kohl, Hulya-Sevcan Daimagueler, Jose Angel Santamaria-Araujo, Max Christoph Liebau, Anne Koy, Sebahattin Cirak, Guenter Schwarz
Summary: Isolated sulfite oxidase deficiency (ISOD) is a rare metabolic disorder caused by mutations in the SUOX gene, leading to a loss of sulfite oxidase (SO) function and accumulation of harmful metabolites, resulting in severe neurodegenerative diseases. The correct insertion of heme cofactor and molybdenum cofactor into SO is crucial for its function, with deficiencies in this process contributing to the development of ISOD.
JOURNAL OF INHERITED METABOLIC DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Martin L. Kirk, Jesse Lepluart, Jing Yang
Summary: Resonance Raman spectroscopy is a powerful tool for studying the geometric and electronic structure of metalloproteins. This review focuses on the enzymes sulfite oxidase, dimethyl sulfoxide reductase, xanthine oxidase, and carbon monoxide dehydrogenase, and highlights how resonance Raman studies have provided detailed insight into the nature of these metalloenzyme active sites.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2022)
Article
Genetics & Heredity
Qi Tian, Yang Cao, Li Shu, Yongjun Chen, Ying Peng, Yaqin Wang, Yuanyuan Chen, Hua Wang, Xiao Mao
Summary: This study reported the first confirmed case of Moco deficiency caused by pathogenic variants in the MOCS3 gene, with the infant displaying typical neurological symptoms and ultimately leading to neonatal death. Compound heterozygous variants in the MOCS3 gene were identified through WES, contributing to genetic diagnosis of Moco deficiency and future genetic counseling.
FRONTIERS IN GENETICS
(2021)
Review
Biochemistry & Molecular Biology
Michel A. Struwe, Axel J. Scheidig, Bernd Clement
Summary: The mitochondrial amidoxime-reducing component (mARC) is a molybdenum enzyme in eukaryotes that activates drugs and reduces compounds. mARC enzymes have been recently studied for their involvement in lipid metabolism and their protective effect against liver disease, but the mechanism remains unknown.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Endocrinology & Metabolism
Alexander Tobias Kaczmarek, Nike Bahlmann, Besarta Thaqi, Patrick May, Guenter Schwarz
Summary: Isolated sulfite oxidase deficiency (ISOD) is a rare hereditary metabolic disease caused by the absence of functional sulfite oxidase (SO) due to mutations of the SUOX gene. Research using exome/genome data from the gnomAD database and published variants has identified 15 novel ISOD-causing SO variants and established a database for future diagnosis of ISOD patients. The study also calculated the first comprehensive incidence rate for ISOD and provided a pathogenicity score for 303 naturally occurring SO missense variants.
MOLECULAR GENETICS AND METABOLISM
(2021)
Article
Chemistry, Multidisciplinary
Anna Olerinyova, Adar Sonn-Segev, Joseph Gault, Cedric Eichmann, Johannes Schimpf, Adrian H. Kopf, Lucas S. P. Rudden, Dzmitry Ashkinadze, Radoslaw Bomba, Lukas Frey, Jason Greenwald, Matteo T. Degiacomi, Ralf Steinhilper, J. Antoinette Killian, Thorsten Friedrich, Roland Riek, Weston B. Struwe, Philipp Kukura
Summary: This study explores the application of mass photometry (MP) to Integral membrane proteins (IMPs) and membrane-mimetic systems at the single-particle level. By applying MP to amphipathic vehicles and lipid nanodiscs, the research characterizes particle size, sample purity, and heterogeneity, enabling high-resolution studies of membrane-protein structure and interactions. Evidence suggests that using native styrenemaleic acid nanodiscs could reveal new insights into the structure of membrane proteins compared to conventional detergent purification methods.
Article
Endocrinology & Metabolism
Ronen Spiegel, Bernd C. Schwahn, Liza Squires, Nils Confer
Summary: Molybdenum cofactor deficiency is a rare genetic disorder that causes sulfite intoxication. Patients with MoCD-A and MoCD-B have a high incidence of symptoms such as seizures and feeding difficulties, and also suffer from severe neurological disabilities. Understanding the natural history of this disease is crucial for evaluating new replacement therapies.
JOURNAL OF INHERITED METABOLIC DISEASE
(2022)
Article
Chemistry, Multidisciplinary
Shahid Hussain, Samuel B. Adeloju
Summary: This study describes the fabrication of a highly selective and ultrasensitive sulfite nanobiosensor using a layered architectural fabrication method. The nanobiosensor exhibits fast response time, wide linear calibration range, and excellent sensitivity, and can be successfully applied to sulfite determination in real samples.
Article
Biochemistry & Molecular Biology
Agnieszka Strzalka, Agnieszka Kois-Ostrowska, Magda Kedra, Tomasz Lebkowski, Grazyna Bieniarz, Marcin J. Szafran, Dagmara Jakimowicz
Summary: Bacterial chromosome topology is regulated by topoisomerases and nucleoid-associated proteins. Streptomyces bacteria utilize the topoisomerase I (TopA) and the HU homologue HupA to maintain chromosome organization and distribution, which is essential for hyphal growth and production of clinically important compounds.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Viktor Kozich, Bernd C. Schwahn, Jitka Sokolova, Michaela Krizkova, Tamas Ditroi, Jakub Krijt, Youssef Khalil, Tomas Krizek, Tereza Vaculikova-Fantlova, Blanka Stiburkova, Philippa Mills, Peter Clayton, Kristyna Barvikova, Holger Blessing, Jolanta Sykut-Cegielska, Carlo Dionisi-Vici, Serena Gasperini, Angeles Garcia-Cazorla, Tobias B. Haack, Tomas Honzik, Pavel Jesina, Alice Kuster, Lucia Laugwitz, Diego Martinelli, Francesco Porta, Rene Santer, Guenter Schwarz, Peter Nagy
Summary: Regulation of H2S homeostasis in humans is not well understood. By studying patients with genetic defects, the importance of certain enzymes in H2S synthesis and catabolism was assessed. The findings suggest the presence of control and compensatory mechanisms in the maintenance of H2S homeostasis.
Article
Cell Biology
Julia Pramio, Mateus Grings, Amanda Gasparin da Rosa, Rafael Teixeira Ribeiro, Nicolas Manzke Glanzel, Marian Flores Signori, Manuela Bianchin Marcuzzo, Larissa Daniele Bobermin, Angela T. S. Wyse, Andre Quincozes-Santos, Moacir Wajner, Guilhian Leipnitz
Summary: Isolated sulfite oxidase (ISOD) and molybdenum cofactor (MoCD) deficiencies are genetic diseases characterized by the accumulation of toxic sulfite in the brain tissues, leading to neurological dysfunction and brain abnormalities in newborns. This study found that sulfite administration caused redox imbalance, mitochondrial dysfunction, and altered signaling proteins in the cerebral cortex of rat pups, which may contribute to the neuropathology of ISOD and MoCD.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Ramapada Dolai, Rahul Kumar, Benedict J. Elvers, Pradeep Kumar Pal, Benson Joseph, Rina Sikari, Mithilesh Kumar Nayak, Avijit Maiti, Tejender Singh, Nicolas Chrysochos, Arumugam Jayaraman, Ivo Krummenacher, Jagannath Mondal, U. Deva Priyakumar, Holger Braunschweig, Cem B. Yildiz, Carola Schulzke, Anukul Jana
Summary: A new type of carbodicarbene (CDC) with two different classes of carbenes has been reported, which shows promising potential as organic electron donors and n-dopants. These compounds exhibit notable redox properties and can form carbon-carbon sigma bonds through reactions with [NO][SbF6].
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Hemant Kumar, Maryam Khosraneh, Siva S. M. Bandaru, Carola Schulzke, Silke Leimkuehler
Summary: This study investigates the reversible oxidation of formate to carbon dioxide catalyzed by molybdenum or tungsten-containing formate dehydrogenases. The formation of bicarbonate as the first intermediate during the reaction at the active site is discovered, contrary to previous reports. Bicarbonate formation occurs after an oxygen atom transfer reaction, where the oxygen is transferred from water to formate, followed by a proton-coupled electron transfer or hydride transfer reaction involving the sulfido ligand as the acceptor.
Article
Chemistry, Organic
Subhadip Jana, Benedict J. Elvers, Sebastian Patsch, Pallavi Sarkar, Ivo Krummenacher, Mithilesh Kumar Nayak, Avijit Maiti, Nicolas Chrysochos, Swapan K. Pati, Carola Schulzke, Holger Braunschweig, Cem B. Yildiz, Anukul Jana
Summary: We developed a new method for synthesizing different quinodimethane derivatives by oxidizing bis-N-heterocyclic olefins linked by pi-conjugated aromatic spacers. Stable diimidazolium para- and ortho-quinodimethane derivatives were obtained with para- and ortho-phenylene bridges, as well as with tetrafluoro-p-phenylene and p-anthracene spacers. The influence of imidazolium substituents on the air and moisture stability of the quinodimethane derivatives was emphasized. Different electron transfer processes were observed depending on the pi-conjugated aromatic spacer used, with two one-electron or one two-electron redox transitions between bis-N-heterocyclic olefins and diimidazolium-quinodimethanes. The formation of pi-conjugated radical-cations, which are transient redox intermediates, was confirmed by EPR investigation.
Article
Biochemistry & Molecular Biology
Moses Olalekan Ogunkola, Gaelle Guiraudie-Capraz, Francois Feron, Silke Leimkuehler
Summary: Sulfur is a crucial element in biomolecules and its incorporation and transfer in humans are facilitated by various sulfurtransferases. One of these sulfurtransferases is human mercaptopyruvate sulfurtransferase (MPST), also known as tRNA thiouridine modification protein (TUM1). TUM1 plays important roles in multiple physiological processes, including Molybdenum cofactor (Moco) biosynthesis, cytosolic tRNA thiolation, and generation of H2S as a signaling molecule in mitochondria and the cytosol.
Article
Chemistry, Physical
Muhammad Ikram, Sadia Rehman, Inayat Feroz, Rizwan Khan, Mutasem Omar Sinnokrot, Fazle Subhan, Muhammad Naeem, Carola Schulzke, Carola Schulzke
Summary: A Schiff base ligand (H-NMDP) was synthesized and reacted with Cu2+ to form a copper complex. The crystal structure of Cu-NMDP reveals a coordination polymer with distorted square planar geometry around copper. The copper complex showed higher activity against glioblastoma cells compared to the ligand alone, suggesting its potential application as a chemotherapy agent.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Chemistry, Organic
Siva Sankar Murthy Bandaru, Carola Schulzke
Summary: The novel organic salt was synthesized through a Lewis acid and Lewis-base reaction and analyzed by various spectroscopic and crystallographic techniques.
Article
Chemistry, Inorganic & Nuclear
Siva Sankar Murthy Bandaru, Claudia Schindler, Felix Wenzek, Carola Schulzke
Summary: Several synthetic cross-coupling procedures were evaluated for tethering pyrazine to dithiocarbonates. The resulting compounds can serve as pro-ligands and can be converted into ene-dithiolate ligand systems resembling molybdopterin by removing the C=O moiety. The coupling of 2-iodopyrazine with stannylated dithiocarbonate units mediated by copper(I)-thiophene-2-carboxylate in stoichiometric equivalents proved to be the most efficient and reliable method for synthesizing the targeted compounds.
Article
Chemistry, Multidisciplinary
Priyanka Saha, Nicolas Chrysochos, Benedict J. Elvers, Sebastian Paetsch, Sk Imraj Uddin, Ivo Krummenacher, Muneshwar Nandeshwar, Anshika Mishra, Karthik V. Raman, Gopalan Rajaraman, Ganesan Prabusankar, Holger Braunschweig, Prince Ravat, Carola Schulzke, Anukul Jana
Summary: A modular approach for the synthesis of isolable crystalline Schlenk hydrocarbon diradicals from m-phenylene bridged electron-rich bis-triazaalkenes as synthons is demonstrated. The diradical nature and triplet electronic structure of the synthesized compounds are confirmed through EPR spectroscopy and computational analysis. The potential of the modular methodology is further illustrated through the utilization of 4,6-dimethyl-m-phenylene as a coupling unit.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Medicinal
Martin Napierkowski, Una Janke, Alena Rong, Mihaela Delcea, Siva Sankar M. Bandaru, Carola Schulzke, Patrick J. Bednarski
Summary: In recent years, the biological properties of pentathiepins have gained attention for their potential in cancer treatment. However, their low solubility and stability limitations have hindered biological evaluation. This study investigated the use of liposomes as drug carriers for pentathiepins to improve solubility and stability. The results showed that the aqueous solubility of pentathiepins increased significantly when incorporated into liposomes, and the stability of pentathiepins in the presence of the antioxidant glutathione was enhanced. Moreover, the liposomal loaded pentathiepins demonstrated comparable anticancer activity to free pentathiepins. In conclusion, liposomes are a suitable carrier for pentathiepins and can improve their solubility and stability without compromising their anticancer activity.
ARCHIV DER PHARMAZIE
(2023)
Review
Chemistry, Inorganic & Nuclear
Siva Sankar Murthy Bandaru, Jagrut Shah, Shatrughn Bhilare, Carola Schulzke, Anant R. Kapdi, Julien Roger, Jean-Cyrille Hierso
Summary: This review focuses on the applications of different ferrocenylphosphine ligands in transition metal-catalyzed cross-coupling strategies, including the asymmetric synthesis using chiral ferrocenyl phosphines. It also discusses the latest advances in the chemistry of symmetric achiral di- and polyphosphine ferrocene-based ligands related to metal-catalyzed bond-forming reactions. A cumulative table compiling significant work in this field is provided.
COORDINATION CHEMISTRY REVIEWS
(2023)
Article
Chemistry, Organic
Jevy V. Correia, Bruno Wilke, Carola Schulzke
Summary: A new alkyne functionalized pterin derivative was successfully synthesized and its purity and chemical structure were confirmed through various methods. The compound can be further modified by utilizing its alkyne moiety and exhibits good solubility in solvents except for water.
Article
Chemistry, Multidisciplinary
Benedict J. Elvers, Sebastian Paetsch, Siva S. M. Bandaru, Vera Krewald, Carola Schulzke, Christian Fischer
Summary: Heteroleptic molybdenum complexes with P2N2 and non-innocent dithiolene ligands were synthesized and electrochemically characterized. The reduction potentials of the complexes were adjusted by ligand-ligand cooperativity via non-covalent interactions. This finding was supported by electrochemical studies, UV/Vis spectroscopy, and temperature-dependent NMR spectroscopy. The observed behavior resembles enzymatic redox modulation through second ligand sphere effects.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Mithilesh Kumar Nayak, Benedict J. Elvers, Debdeep Mandal, Ayan Das, Raghunathan Ramakrishnan, Kaustubh R. Mote, Carola Schulzke, Cem Burak Yildiz, Anukul Jana
Summary: The reduction of 2-H-substituted pyrrolinium cations results in dimerisation or H-abstracted products, depending on the N-substituents. The dimerised 2,2'-bipyrrolidine derivatives with a central carbon-carbon single bond are stable and can be oxidised chemically or electrochemically. These dimers, which are air and moisture-stable, can serve as a source of two electrons in various chemical transformations.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Nicolas Chrysochos, Sebastian Paetsch, Benedict J. Elvers, Ivo Krummenacher, Muneshwar Nandeshwar, Ganesan Prabusankar, Holger Braunschweig, Carola Schulzke, Prince Ravat, Anukul Jana
Summary: The synthesis of a twisted, push-pull, and electron-rich alkene is reported, providing a unique combination for alkene compounds. This newly synthesized alkene motif was used as a donor for the synthesis of a boron-containing pi-conjugated compound with zwitterionic properties through intramolecular charge transfer.
CHEMICAL COMMUNICATIONS
(2023)