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1.
Anthony John Pastore Alvaro Montoya Manasi Kamat Kari B. Basso James S. Italia Abhishek Chatterjee Maria Drosou Dimitrios A. Pantazis Alexander Angerhofer 《Protein science : a publication of the Protein Society》2023,32(1):e4537
Oxalate decarboxylase from Bacillus subtilis is a binuclear Mn-dependent acid stress response enzyme that converts the mono-anion of oxalic acid into formate and carbon dioxide in a redox neutral unimolecular disproportionation reaction. A π-stacked tryptophan dimer, W96 and W274, at the interface between two monomer subunits facilitates long-range electron transfer between the two Mn ions and plays an important role in the catalytic mechanism. Substitution of W96 with the unnatural amino acid 5-hydroxytryptophan leads to a persistent EPR signal which can be traced back to the neutral radical of 5-hydroxytryptophan with its hydroxyl proton removed. 5-Hydroxytryptophan acts as a hole sink preventing the formation of Mn(III) at the N-terminal active site and strongly suppresses enzymatic activity. The lower boundary of the standard reduction potential for the active site Mn(II)/Mn(III) couple can therefore be estimated as 740 mV against the normal hydrogen electrode at pH 4, the pH of maximum catalytic efficiency. Our results support the catalytic importance of long-range electron transfer in oxalate decarboxylase while at the same time highlighting the utility of unnatural amino acid incorporation and specifically the use of 5-hydroxytryptophan as an energetic sink for hole hopping to probe electron transfer in redox proteins. 相似文献
2.
Christos E. Zois Anne M. Hendriks Syed Haider Elisabete Pires Esther Bridges Dimitra Kalamida Dimitrios Voukantsis B. Christoffer Lagerholm Rudolf S. N. Fehrmann Wilfred F. A. den Dunnen Andrei I. Tarasov Otto Baba John Morris Francesca M. Buffa James S. O. McCullagh Mathilde Jalving Adrian L. Harris 《Cell death & disease》2022,13(6)
Channelling of glucose via glycogen, known as the glycogen shunt, may play an important role in the metabolism of brain tumours, especially in hypoxic conditions. We aimed to dissect the role of glycogen degradation in glioblastoma (GBM) response to ionising radiation (IR). Knockdown of the glycogen phosphorylase liver isoform (PYGL), but not the brain isoform (PYGB), decreased clonogenic growth and survival of GBM cell lines and sensitised them to IR doses of 10–12 Gy. Two to five days after IR exposure of PYGL knockdown GBM cells, mitotic catastrophy and a giant multinucleated cell morphology with senescence-like phenotype developed. The basal levels of the lysosomal enzyme alpha-acid glucosidase (GAA), essential for autolysosomal glycogen degradation, and the lipidated forms of gamma-aminobutyric acid receptor-associated protein-like (GABARAPL1 and GABARAPL2) increased in shPYGL U87MG cells, suggesting a compensatory mechanism of glycogen degradation. In response to IR, dysregulation of autophagy was shown by accumulation of the p62 and the lipidated form of GABARAPL1 and GABARAPL2 in shPYGL U87MG cells. IR increased the mitochondrial mass and the colocalisation of mitochondria with lysosomes in shPYGL cells, thereby indicating reduced mitophagy. These changes coincided with increased phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase 2, slower ATP generation in response to glucose loading and progressive loss of oxidative phosphorylation. The resulting metabolic deficiencies affected the availability of ATP required for mitosis, resulting in the mitotic catastrophy observed in shPYGL cells following IR. PYGL mRNA and protein levels were higher in human GBM than in normal human brain tissues and high PYGL mRNA expression in GBM correlated with poor patient survival. In conclusion, we show a major new role for glycogen metabolism in GBM cancer. Inhibition of glycogen degradation sensitises GBM cells to high-dose IR indicating that PYGL is a potential novel target for the treatment of GBMs.Subject terms: Cancer metabolism, CNS cancer 相似文献
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ABSTRACT: INTRODUCTION: Adenoid cystic cancer of the breast is a rare condition, and even rarer are the cases where it is histologically mixed with other variants of cancer within a single lesion. In this report, one of the few cases of mixed adenoid cystic breast cancer intermingled with the infiltrating ductal variant is presented. A subsequent review of the relevant literature presents the existing experience in treating mixed breast cancers with adenoid cystic components with regard to diagnosis, treatment, and prognosis. CASE PRESENTATION: We describe a case of mixed adenoid cystic cancer of the breast with infiltrating ductal carcinoma in a 67-year-old Caucasian woman who underwent mastectomy with sentinel node biopsy. CONCLUSION: Surgery remains the cornerstone of treatment of these patients, and radiotherapy is administered when breast-conserving treatment is undertaken or a large tumor with affected lymph nodes is present. Hormonal treatment does not have a role, as estrogen receptors are always absent from both tumor components. Chemotherapy is nearly always administered on the basis of estrogen receptor and progesterone negativity and the more aggressive potential of the non-adenoid cystic component. The de-differentiation of an indolent type of cancer to a more aggressive one may affect the prognosis. 相似文献
5.
Susanne Siebentritt Enrico Avancini Marcus Br Jakob Bombsch Emilie Bourgeois Stephan Buecheler Romain Carron Celia Castro Sebastien Duguay Roberto Flix Evelyn Handick Dimitrios Hariskos Ville Havu Philip Jackson Hannu‐Pekka Komsa Thomas Kunze Maria Malitckaya Roberto Menozzi Milos Nesladek Nicoleta Nicoara Martti Puska Mohit Raghuwanshi Philippe Pareige Sascha Sadewasser Giovanna Sozzi Ayodhya Nath Tiwari Shigenori Ueda Arantxa Vilalta‐Clemente Thomas Paul Weiss Florian Werner Regan G. Wilks Wolfram Witte Max Hilaire Wolter 《Liver Transplantation》2020,10(8)
6.
Amy E. Zanne Kessy Abarenkov Michelle E. Afkhami Carlos A. Aguilar‐Trigueros Scott Bates Jennifer M. Bhatnagar Posy E. Busby Natalie Christian William K. Cornwell Thomas W. Crowther Habacuc Flores‐Moreno Dimitrios Floudas Romina Gazis David Hibbett Peter Kennedy Daniel L. Lindner Daniel S. Maynard Amy M. Milo Rolf Henrik Nilsson Jeff Powell Mark Schildhauer Jonathan Schilling Kathleen K. Treseder 《Biological reviews of the Cambridge Philosophical Society》2020,95(2):409-433
Fungi play many essential roles in ecosystems. They facilitate plant access to nutrients and water, serve as decay agents that cycle carbon and nutrients through the soil, water and atmosphere, and are major regulators of macro‐organismal populations. Although technological advances are improving the detection and identification of fungi, there still exist key gaps in our ecological knowledge of this kingdom, especially related to function . Trait‐based approaches have been instrumental in strengthening our understanding of plant functional ecology and, as such, provide excellent models for deepening our understanding of fungal functional ecology in ways that complement insights gained from traditional and ‐omics‐based techniques. In this review, we synthesize current knowledge of fungal functional ecology, taxonomy and systematics and introduce a novel database of fungal functional traits (FunFun). FunFun is built to interface with other databases to explore and predict how fungal functional diversity varies by taxonomy, guild, and other evolutionary or ecological grouping variables. To highlight how a quantitative trait‐based approach can provide new insights, we describe multiple targeted examples and end by suggesting next steps in the rapidly growing field of fungal functional ecology. 相似文献
7.
Tsikas Dimitrios Bollenbach Alexander Hanff Erik Beckmann Bibiana Redfors Bjrn 《Amino acids》2020,52(2):235-245
Amino Acids - Low L-homoarginine (hArg) concentrations in human blood and urine are associated with renal and cardiovascular morbidity and mortality, yet the underlying mechanisms and the... 相似文献
8.
Rucha Karnik Christopher Grefen Robert Bayne Annegret Honsbein Tim K?hler Dimitrios Kioumourtzoglou Mary Williams Nia J. Bryant Michael R. Blatt 《The Plant cell》2013,25(4):1368-1382
The Arabidopsis thaliana Qa-SNARE SYP121 (=SYR1/PEN1) drives vesicle traffic at the plasma membrane of cells throughout the vegetative plant. It facilitates responses to drought, to the water stress hormone abscisic acid, and to pathogen attack, and it is essential for recovery from so-called programmed stomatal closure. How SYP121-mediated traffic is regulated is largely unknown, although it is thought to depend on formation of a fusion-competent SNARE core complex with the cognate partners VAMP721 and SNAP33. Like SYP121, the Arabidopsis Sec1/Munc18 protein SEC11 (=KEULE) is expressed throughout the vegetative plant. We find that SEC11 binds directly with SYP121 both in vitro and in vivo to affect secretory traffic. Binding occurs through two distinct modes, one requiring only SEC11 and SYP121 and the second dependent on assembly of a complex with VAMP721 and SNAP33. SEC11 competes dynamically for SYP121 binding with SNAP33 and VAMP721, and this competition is predicated by SEC11 association with the N terminus of SYP121. These and additional data are consistent with a model in which SYP121-mediated vesicle fusion is regulated by an unusual “handshaking” mechanism of concerted SEC11 debinding and rebinding. They also implicate one or more factors that alter or disrupt SEC11 association with the SYP121 N terminus as an early step initiating SNARE complex formation. 相似文献
9.
Rajendra Boggavarapu Jean-Marc Jeckelmann Daniel Harder Philipp Schneider Z?hre Ucurum Matthias Hediger Dimitrios Fotiadis 《PloS one》2013,8(10)
Expression and purification of human membrane proteins for structural studies represent a great challenge. This is because micro- to milligram amounts of pure isolated protein are required. To this aim, we successfully expressed the human vitamin C transporter-1 (hSVCT1; SLC23A1) in Xenopus laevis oocytes and isolated highly pure protein in microgram amounts. Recombinant hSVCT1 was functional when expressed in oocytes and glycosylated. Structural analysis of purified hSVCT1 by transmission electron microscopy and single particle analysis unveiled its shape, dimensions and low-resolution structure as well as the existence of a major monomeric and minor dimeric population. Chemical crosslinking of isolated oocyte membranes containing expressed hSVCT1 indicated similar oligomeric states of hSVCT1 in lipid bilayers. This work reports the first purification and structural analysis of a human SVCT protein and opens the way for future functional and structural studies using purified hSVCT1. 相似文献
10.
Dimitrios Paraskevis Georgios Nikolopoulos Anastasios Fotiou Chrissa Tsiara Dimitra Paraskeva Vana Sypsa Marios Lazanas Panagiotis Gargalianos Mina Psichogiou Athanasios Skoutelis Lucas Wiessing Samuel R. Friedman Don C. d. e. s. Jarlais Manina Terzidou Jenny Kremastinou Meni Malliori Angelos Hatzakis 《PloS one》2013,8(11)