Proteostasis in thermogenesis and obesity.
Authors: Bartelt A, Widenmaier SB Abstract The proper production, degradation, folding and activity of proteins, proteostasis, is essential for any cellular function. From single cell organisms to humans, selective pressures have led to the evolution of adaptive programs that ensure proteins are properly produced and disposed of when necessary. Environmental factors such as temperature, nutrient availability, pathogens as well as predators have greatly influenced the development of mechanisms such the unfolded protein response, endoplasmic reticulum-associated protein degradation and autophagy, working together in ...
Source: Biological Chemistry - February 16, 2020 Category: Chemistry Tags: Biol Chem Source Type: research

The biogenesis of mitochondrial intermembrane space proteins.
Authors: Edwards R, Gerlich S, Tokatlidis K Abstract The mitochondrial intermembrane space (IMS) houses a large spectrum of proteins with distinct and critical functions. Protein import into this mitochondrial sub-compartment is underpinned by an intriguing variety of pathways, many of which are still poorly understood. The constricted volume of the IMS and the topological segregation by the inner membrane cristae into a bulk area surrounded by the boundary inner membrane and the lumen within the cristae is an important factor that adds to the complexity of the protein import, folding and assembly processes. We dis...
Source: Biological Chemistry - February 16, 2020 Category: Chemistry Tags: Biol Chem Source Type: research

Heat shock protein 60 is a disease-associated sialoglycoprotein in human non-small cell lung cancer.
Authors: Singh P, Kumari M, Bal A, Srinivasan R, Ghosh S Abstract The diagnostic and therapeutic potential of Maackia amurensis agglutinin (MAA) have been reported in various malignancies. Earlier, we have found that MAA specifically interacted with human non-small cell lung-cancer (NSCLC) cells and induced apoptosis in these cells. The present study was designed to identify Maackia amurensis leukoagglutinin (MAL-I, one of the components of MAA, having same carbohydrate specificity as MAA) interacting membrane sialoglycoprotein(s) of two subtypes of human NSCLC cell lines. Nine proteins were identified using 2D-PAG...
Source: Biological Chemistry - February 14, 2020 Category: Chemistry Tags: Biol Chem Source Type: research

Small-molecule modulation of p53 protein-protein interactions.
Authors: Kuusk A, Boyd H, Chen H, Ottmann C Abstract Small molecule modulation of protein-protein interactions is a very promising but also challenging area in drug discovery. The tumor suppressor protein p53 is one of the most frequently altered proteins in human cancers, making it an attractive target in oncology. 14-3-3 proteins have been shown to bind to and positively regulate p53 activity by protecting it from MDM2-dependent degradation or activating its DNA binding affinity. Protein-protein interactions can be modulated by inhibiting or stabilizing specific interactions by small molecules. Whereas inhibition...
Source: Biological Chemistry - February 14, 2020 Category: Chemistry Tags: Biol Chem Source Type: research

The endoplasmic reticulum-mitochondria encounter structure: coordinating lipid metabolism across membranes.
Authors: Kornmann B Abstract Endosymbiosis, the beginning of a collaboration between an Archaeon and a Bacterium and founding step in the evolution of Eukaryotes, owes its success to the establishment of communication routes between the host and the symbiont to allow the exchange of metabolites. As far as lipids are concerned, it is the host that has learnt the symbiont's language, as eukaryote lipids appear to have been borrowed from the bacterial symbiont. Mitochondria exchange lipids with the rest of the cell at membrane contact sites. In fungi, the Endoplasmic Reticulum-Mitochondria Encounter Structure (ERMES) ...
Source: Biological Chemistry - February 14, 2020 Category: Chemistry Tags: Biol Chem Source Type: research

Volatilomes of Cyclocybe aegerita during different stages of monokaryotic and dikaryotic fruiting.
Authors: Orban A, Hennicke F, Rühl M Abstract Volatile organic compounds (VOC) are characteristic for different fungal species. However, little is known about VOC changes during development and their biological role. Therefore, we established a laboratory cultivation system in modified crystallizing dishes for analyzing VOC during fruiting body development of the dikaryotic strain Cyclocybe aegerita AAE-3 as well as four monokaryotic offspring siblings exhibiting different fruiting phenotypes. From these, VOC were extracted directly from the headspace (HS) and analyzed by means of gas chromatography-mass spect...
Source: Biological Chemistry - February 12, 2020 Category: Chemistry Tags: Biol Chem Source Type: research

EZH2 function in immune cell development.
Authors: Nutt SL, Keenan C, Chopin M, Allan RS Abstract The polycomb repressive complex 2 (PRC2) consists of three core components EZH2, SUZ12 and EED. EZH2 catalyzes the methylation of lysine 27 of histone H3, a modification associated with gene silencing. Through gene duplication higher vertebrate genomes also encode a second partially redundant methyltransferase, EZH1. Within the mammalian immune system most research has concentrated on EZH2 which is expressed predominantly in proliferating cells. EZH2 and other PRC2 components are required for hematopoietic stem cell function and lymphocyte development, at leas...
Source: Biological Chemistry - February 12, 2020 Category: Chemistry Tags: Biol Chem Source Type: research

Biogenesis pathways of α-helical mitochondrial outer membrane proteins.
Biogenesis pathways of α-helical mitochondrial outer membrane proteins. Biol Chem. 2019 Dec 01;: Authors: Drwesh L, Rapaport D Abstract Mitochondria harbor in their outer membrane (OM) proteins of different topologies. These proteins are encoded by the nuclear DNA, translated on cytosolic ribosomes and inserted into their target organelle by sophisticated protein import machineries. Recently, considerable insights have been accumulated on the insertion pathways of proteins into the mitochondrial OM. In contrast, little is known regarding the early cytosolic stages of their biogenesis. It is gener...
Source: Biological Chemistry - February 6, 2020 Category: Chemistry Tags: Biol Chem Source Type: research

Porins as helpers in mitochondrial protein translocation.
Authors: Grevel A, Becker T Abstract Mitochondria import the vast majority of their proteins via dedicated protein machineries. The translocase of the outer membrane (TOM complex) forms the main entry site for precursor proteins that are produced on cytosolic ribosomes. Subsequently, different protein sorting machineries transfer the incoming preproteins to the mitochondrial outer and inner membrane, the intermembrane space and the matrix. In this review, we highlight the recently discovered role of porin, also termed voltage-dependent anion channel (VDAC), in mitochondrial protein biogenesis. Porin forms the major...
Source: Biological Chemistry - January 23, 2020 Category: Chemistry Tags: Biol Chem Source Type: research

Asymmetric inheritance of mitochondria in yeast.
Authors: Klecker T, Westermann B Abstract Mitochondria are essential organelles of virtually all eukaryotic organisms. As they cannot be made de novo, they have to be inherited during cell division. In this review, we provide an overview on mitochondrial inheritance in Saccharomyces cerevisiae, a powerful model organism to study asymmetric cell division. Several processes have to be coordinated during mitochondrial inheritance: Mitochondrial transport along the actin cytoskeleton into the emerging bud is powered by a myosin motor protein; cell cortex anchors retain a critical fraction of mitochondria in the mother ...
Source: Biological Chemistry - January 23, 2020 Category: Chemistry Tags: Biol Chem Source Type: research

What you see is what you get: activity-based probes in single-cell analysis of enzymatic activities.
Authors: Lentz CS Abstract Molecular imaging methods can provide spatio-temporal information about the distribution of biomolecules or biological processes, such as certain enzymatic activities, in single cells. Within a cell, it is possible to define the subcellular location of a target, its trafficking through the cell, colocalization with other biomolecules of interest and involvement in certain cell biological processes. On the other hand, single-cell imaging promises to distinguish cells that are phenotypically different from each other. The corresponding cellular diversity comprises the presence of functional...
Source: Biological Chemistry - January 16, 2020 Category: Chemistry Tags: Biol Chem Source Type: research

Characterization of substrate specificity and novel autoprocessing mechanism of dipeptidase A from Prevotella intermedia.
In conclusion, the marked Arg-MCA-hydrolyzing activity in Pre. intermedia was mediated by BAU17746 belonging to the C69-family dipeptidase A, in which the mature form carries an essential cysteine at the N-terminus. PMID: 31913843 [PubMed - as supplied by publisher] (Source: Biological Chemistry)
Source: Biological Chemistry - January 10, 2020 Category: Chemistry Tags: Biol Chem Source Type: research

Septin architecture and function in budding yeast.
Authors: Farkašovský M Abstract The septins constitute a conserved family of guanosine phosphate-binding and filamentforming proteins widespread across eukaryotic species. Septins appear to have two principal functions. One is to form a cortical diffusion barrier, like the septin collar at the bud neck of Saccharomyces cerevisiae, which prevents movement of membrane-associated proteins between the mother and daughter cells. The second is to serve as a polymeric scaffold for recruiting the proteins required for critical cellular processes to particular subcellular areas. In the last decade, structural ...
Source: Biological Chemistry - January 10, 2020 Category: Chemistry Tags: Biol Chem Source Type: research

Human papillomavirus oncoproteins and post translational modifications: generating multifunctional hubs for overriding cellular homeostasis.
Authors: Basukala O, Sarabia-Vega V, Banks L Abstract Human Papillomaviruses are major human carcinogens, causing around 5% of all human cancers, with cervical cancer being the most important. These tumours are all driven by the two HPV oncoproteins E6 and E7. Whilst their mechanisms of action are becoming increasingly clear through their abilities to target essential cellular tumour suppressor and growth control pathways, the roles that post-translational modifications of E6 and E7 plays in the regulation of these activities remains unclear. Here we discuss the direct consequences of some of the most common post t...
Source: Biological Chemistry - January 10, 2020 Category: Chemistry Tags: Biol Chem Source Type: research

The redox status of cysteine thiol residues of apolipoprotein E impacts on its lipid interactions.
In this report, the influence of modification of Cys thiols in apoE2 and apoE3 on interactions with lipids was investigated. The apoE redox status was examined by a band-shift assay using a maleimide compound, and interactions with lipids were evaluated by a kinetic assay using dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and non-denaturing PAGE. A reduction in DMPC clearance activity of apoE2 and apoE3 but not apoE4 was observed. Although hydrogen peroxideinduced oxidation decreased the clearance activity of the isoforms, apoE2 showed the greatest residual activity. Both Cys-thiol masking and dimerization decreased the ...
Source: Biological Chemistry - January 10, 2020 Category: Chemistry Tags: Biol Chem Source Type: research

LncRNA MEG3 inhibits HMEC-1 cells growth, migration and tube formation via sponging miR-147.
Authors: Xu D, Liu T, He L, Han D, Ma Y, Du J Abstract Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) has been identified as a regulatory molecular in angiogenesis. The goal of this study is to illustrate how MEG3 affects the angiogenesis of vascular endothelial cells. Expression of MEG3, miR-147, and intracellular cell adhesion molecule-1 (ICAM-1) in human microvascular endothelial cell line (HMEC-1) was altered by transfection, then cell viability, apoptosis, migration, tube formation, as well as the correlation among MEG3, miR-147 and ICAM-1 were explored. MEG3 was down-regulated during tube for...
Source: Biological Chemistry - December 23, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Power to the daughters - mitochondrial and mtDNA transmission during cell division.
Authors: Aretz I, Jakubke C, Osman C Abstract Mitochondria supply virtually all eukaryotic cells with energy through ATP production by oxidative phosphoryplation (OXPHOS). Accordingly, maintenance of mitochondrial function is fundamentally important to sustain cellular health and various diseases have been linked to mitochondrial dysfunction. Biogenesis of OXPHOS complexes crucially depends on mitochondrial DNA (mtDNA) that encodes essential subunits of the respiratory chain and is distributed in multiple copies throughout the mitochondrial network. During cell division, mitochondria, including mtDNA, need to be ac...
Source: Biological Chemistry - December 11, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Bioenergetics and translational metabolism: implications for genetics, physiology and precision medicine.
Authors: Hill BG, Shiva S, Ballinger S, Zhang J, Darley-Usmar VM Abstract It is now becoming clear that human metabolism is extremely plastic and varies substantially between healthy individuals. Understanding the biochemistry that underlies this physiology will enable personalized clinical interventions related to metabolism. Mitochondrial quality control and the detailed mechanisms of mitochondrial energy generation are central to understanding susceptibility to pathologies associated with aging including cancer, cardiac and neurodegenerative diseases. A precision medicine approach is also needed to evaluate the ...
Source: Biological Chemistry - December 11, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Different signaling and functionality of Rac1 and Rac1b in the progression of lung adenocarcinoma.
Authors: Seiz JR, Klinke J, Scharlibbe L, Lohfink D, Heipel M, Ungefroren H, Giehl K, Menke A Abstract Rac1 is a ubiquitously expressed Rho GTPase and an important regulator of the actin cy-toskeleton. Its splice variant Rac1b exhibits a 19aa in-frame insertion and is predominantly active. Both proteins were described in tumorigenesis or metastasis. We investigated the contribution of Rac1 and Rac1b to tumor progression of human non-small-cell-lungadenocarcinoma (NSCLA). Rac1 protein was present in 8/8 NSCLA cell lines analyzed, whereas Rac1b was expressed in only 6/8. In wound healing assays, EGFP-Rac1 slightly de...
Source: Biological Chemistry - December 9, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Dr. NO and Mr. Toxic - the versatile role of nitric oxide.
Authors: Tran SL, Porrini C, Ramarao N Abstract Nitric oxide (NO) is present in various organisms from humans, to plants, fungus and bacteria. NO is a fundamental signaling molecule implicated in major cellular functions. The role of NO ranges from an essential molecule to a potent mediator of cellular damages. The ability of NO to react with a broad range of bio molecules allows on one hand its regulation and a gradient concentration and on the other hand to exert physiological as well as pathological functions. In humans, NO is implicated in cardiovascular homeostasis, neurotransmission and immunity. However, NO ...
Source: Biological Chemistry - December 9, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Diffuse or hitch a ride: how photoreceptor lipidated proteins get from here to there.
Authors: Frederick JM, Hanke-Gogokhia C, Ying G, Baehr W Abstract Photoreceptors are polarized neurons, with specific subcellular compartmentalization and unique requirements for protein expression and trafficking. Each photoreceptor contains an outer segment (OS) where vision begins, an inner segment (IS) where protein synthesis occurs, and a synaptic terminal for signal transmission to second-order neurons. The OS is a large, modified primary cilium attached to the IS by a slender connecting cilium, the equivalent of the transition zone (TZ). Daily renewal of ~10% of the OS requires massive protein biosynthesis i...
Source: Biological Chemistry - December 9, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Aha-type co-chaperones: the alpha or the omega of the Hsp90 ATPase cycle?
Authors: LaPointe P, Mercier R, Wolmarans A Abstract Heat shock protein 90 (Hsp90) is a dimeric molecular chaperone that plays an essential role in cellular homeostasis. It functions in the context of a structurally dynamic ATP-dependent cycle to promote conformational changes in its clientele to aid stability, maturation, and activation. The client activation cycle is tightly regulated by a cohort of co-chaperone proteins that display specific binding preferences for certain conformations of Hsp90, guiding Hsp90 through its functional ATPase cycle. Aha-type co-chaperones are well-known to robustly stimulate the AT...
Source: Biological Chemistry - November 30, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Developments in anticancer vaccination: budding new adjuvants.
Authors: Santos-Sierra S Abstract The immune system has a limited capacity to recognize and fight cells that become cancerous. Therapeutic vaccination of cancer is a promising strategy whose success depends on a powerful activation of the cells of the adaptive immune system specific for tumor-cell detection and killing (e.g. CD4+ and CD8+ T-cells). In cancer patients, the immune system has to seek the right balance between cancer rejection and host-immunosuppression. The tumor milieu builds a protective shell and tumor cells rapidly accumulate mutations what promotes antigen variability and immune-escape. In the la...
Source: Biological Chemistry - November 30, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Inorganic nitrite bioactivation and role in physiological signaling and therapeutics.
Authors: Amdahl MB, DeMartino AW, Gladwin MT Abstract The bioactivation of inorganic nitrite refers to the conversion of otherwise 'inert' nitrite to the diatomic signaling molecule nitric oxide (NO), which plays important roles in human physiology and disease, notably in the regulation of vascular tone and blood flow. While the most well-known sources of NO are the nitric oxide synthase (NOS) enzymes, another source of NO is the nitrate-nitrite-NO pathway, whereby nitrite (obtained from reduction of dietary nitrate) is further reduced to form NO. The past few decades have seen extensive study of the mechanisms of ...
Source: Biological Chemistry - November 21, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Circular RNA hsa_circ_0001178 facilitates the invasion and metastasis of colorectal cancer through upregulating ZEB1 via sponging multiple miRNAs.
Authors: Ren C, Zhang Z, Wang S, Zhu W, Zheng P, Wang W Abstract Metastasis is the main cause of increasing cancer morbidity and mortality. However, the underlying mechanism of cancer metastasis remains largely unknown. In the present study, we identified one circular RNA (circRNA) closely related to the metastasis of colorectal cancer (CRC), namely hsa_circ_0001178. CRC patients with high hsa_circ_0001178 were more prone to have metastatic clinical features, advanced TNM stage and adverse prognosis. Stable knockdown of hsa_circ_0001178 significantly weakened CRC cell migratory and invasive capabilities in vitro as...
Source: Biological Chemistry - November 21, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

The cGMP system: components and function.
This article does not intend an in depth review of this system. Signal transduction by cGMP is controlled by the generating enzymes guanylyl cyclases, the degrading enzymes phosphodiesterases, and the cGMP regulated enzymes cyclic nucleotide gated ion channels, cGMP-dependent protein kinases and cGMP-regulated phosphodiesterases. Part A gives a very concise introduction to the components. Part B gives a very concise introduction to the functions modulated by cGMP. The article cites many recent reviews for those, who want a deeper insight. PMID: 31747372 [PubMed - as supplied by publisher] (Source: Biological Chemistry)
Source: Biological Chemistry - November 21, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Derlin-1 functions as a growth promoter in breast cancer.
In this study, we found that Derlin-1 overexpression was higher in breast cancer compared to normal samples through TCGA and GTEx database analyses. Kaplan-Meier plotter analysis showed that Derlin-1 was a predicting factor for patient prognosis. Derlin-1 expression was significantly up-regulated in breast cancer tissues (18/30, 60.00%) compared to corresponding paracancerous tissue (9/30, 30.00%, p 
Source: Biological Chemistry - November 14, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Hsa-miR-6165 downregulates insulin-like growth factor-1 receptor (IGF-1R) expression and enhances apoptosis in SW480 cells.
Authors: Hassanlou M, Soltani BM, Medlej A, Kay M, Mowla SJ Abstract MicroRNAs are small non-coding RNAs that are implicated in various biological processes. Hsa-miR-6165 (miR-6165), located in the p75NTR gene, is known to induce apoptosis in human cell lines, but its mechanism of action is not fully understood yet. Here, we predicted the insulin-like growth factor 1 receptor (IGF-1R) gene as a bona fide target for miR-6165. The overexpression of miR-6165 in SW480 cells resulted in significant downregulation of IGF-1R expression as detected by real time quantitative polymerase chain reaction (RT-qPCR) and enzyme-li...
Source: Biological Chemistry - November 10, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Aberrant mitochondrial bioenergetics in the cerebral cortex of the Fmr1 knockout mouse model of fragile X syndrome.
Authors: D'Antoni S, de Bari L, Valenti D, Borro M, Bonaccorso CM, Simmaco M, Vacca RA, Catania MV Abstract Impaired energy metabolism may play a role in the pathogenesis of neurodevelopmental disorders including fragile X syndrome (FXS). We checked brain energy status and some aspects of cell bioenergetics, namely the activity of key glycolytic enzymes, glycerol-3-phosphate shuttle and mitochondrial respiratory chain (MRC) complexes, in the cerebral cortex of the Fmr1 knockout (KO) mouse model of FXS. We found that, despite a hyperactivation of MRC complexes, adenosine triphosphate (ATP) production via mitochondri...
Source: Biological Chemistry - November 10, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Happy Birthday: Biological Chemistry is celebrating its 400th volume.
Authors: Brüne B PMID: 31693490 [PubMed - as supplied by publisher] (Source: Biological Chemistry)
Source: Biological Chemistry - November 9, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Ribosome recycling in mRNA translation, quality control, and homeostasis.
Authors: Nürenberg-Goloub E, Tampé R Abstract Protein biosynthesis is a conserved process, essential for life. Ongoing research for four decades has revealed the structural basis and mechanistic details of most protein biosynthesis steps. Numerous pathways and their regulation have recently been added to the translation system describing protein quality control and mRNA surveillance, ribosome-associated protein folding and post-translational modification as well as human disorders associated with mRNA and ribosome homeostasis. Thus, translation constitutes a key regulatory process placing the ribosome a...
Source: Biological Chemistry - October 31, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Intracellular distribution of pseudorabies virus UL2 and detection of its nuclear import mechanism.
Authors: Li M, Xu Z, Zou X, Wang Y, Li Y, Ou X, Deng Y, Guo Y, Gan W, Chen D, Peng T, Xiao J, Cai M Abstract Pseudorabies virus (PRV) UL2 (pUL2) is a multifunctional protein, which is homologous with herpes simplex virus 1 early protein UL2 (hUL2) and crucial for the viral propagation. Yet, how pUL2 executes its roles in the viral life cycle remain inadequately understood. In order to uncover its effect on the procedure of PRV infection, investigation was performed to examine the subcellular distribution of pUL2 and establish its trafficking mechanism. In the present study, enhanced yellow fluorescent protein or My...
Source: Biological Chemistry - October 31, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Platelets as a "natural factory" for growth factor production that sustains normal (and pathological) cell biology.
Platelets as a "natural factory" for growth factor production that sustains normal (and pathological) cell biology. Biol Chem. 2019 Oct 01;: Authors: Andrade SS, Sousa Faria AV, Paulo Queluz D, Ferreira-Halder CV Abstract Platelets have attracted substantial attention in the current decade owing to their unexpected pleiotropic properties and conflicted functions. In fact, platelets participate in both health (haemostasis) and disease (thrombotic diseases). Much of the plasticity of platelets come from the fact that platelets are the reservoir and the "natural factory" of growth fact...
Source: Biological Chemistry - October 31, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Proteasomes: unfoldase-assisted protein degradation machines.
Authors: Majumder P, Baumeister W Abstract Proteasomes are the principal molecular machines for the regulated degradation of intracellular proteins. These self-compartmentalized macromolecular assemblies selectively degrade misfolded, mistranslated, damaged or otherwise unwanted proteins, and play a pivotal role in the maintenance of cellular proteostasis, in stress response, and numerous other processes of vital importance. Whereas the molecular architecture of the proteasome core is universally conserved, the unfoldase modules vary in overall structure, subunit complexity, and regulatory principles. Proteasomal u...
Source: Biological Chemistry - October 31, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Transport mechanism of Mycobacterium tuberculosis MmpL/S family proteins and implications in pharmaceutical targeting.
This article summarizes the structure, function, phylogenetics of M. tuberculosis MmpL/S proteins and their roles in host immune response, inhibitors and regulatory system. PMID: 31652116 [PubMed - as supplied by publisher] (Source: Biological Chemistry)
Source: Biological Chemistry - October 30, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Identification of new probe substrates for human CYP20A1.
Authors: Durairaj P, Fan L, Sharma SS, Jie Z, Bureik M Abstract CYP20A1 is a well-conserved member of the human cytochrome P450 enzyme family for which no endogenous or xenobiotic substrate is known. We have recently shown that this enzyme has moderate activity towards two proluciferin probe substrates. In order to facilitate the search for physiological substrates we have tested nine additional proluciferins in this study and identified three such probe substrates that give much higher product yields. Using one of these probes, we demonstrate inhibition of CYP20A1 activity by 1-benzylimidazole, ketoconazole and le...
Source: Biological Chemistry - October 30, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Synthetic and biological approaches to map substrate specificities of proteases.
Authors: Chen S, Yim JJ, Bogyo M Abstract Proteases are regulators of diverse biological pathways including protein catabolism, antigen processing and inflammation, as well as various diseases conditions, such as malignant metastasis, viral infection, and parasite invasion. The identification of substrates of a given protease is essential to understand its function and this information can also aid in the design of specific inhibitors and active site probes. However, the diversity of putative protein and peptide substrates makes connecting a protease to its downstream substrates technically difficult and time-consu...
Source: Biological Chemistry - October 24, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Converting GTP hydrolysis into motion: versatile translational elongation factor G.
Authors: Rodnina MV, Peske F, Peng BZ, Belardinelli R, Wintermeyer W Abstract Elongation factor G (EF-G) is a translational GTPase that acts at several stages of protein synthesis. Its canonical function is to catalyze tRNA movement during translation elongation, but it also acts at the last step of translation to promote ribosome recycling. Moreover, EF-G has additional functions, such as helping the ribosome to maintain the mRNA reading frame or to slide over non-coding stretches of the mRNA. EF-G has an unconventional GTPase cycle that couples the energy of GTP hydrolysis to movement. EF-G facilitates movement i...
Source: Biological Chemistry - October 11, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

The Ras switch in structural and historical perspective.
Authors: Gasper R, Wittinghofer F Abstract Since its discovery as an oncogene more than 40 years ago, Ras has been and still is in the focus of many academic and pharmaceutical labs around the world. A huge amount of work has accumulated on its biology. However, many questions about the role of the different Ras isoforms in health and disease still exist and a full understanding will requiremore intensive work in the future. Here we try to survey some of the structural findings in a historical perspective and how it has influenced our understanding of structure-function and mechanistic relationships of Ras and its ...
Source: Biological Chemistry - October 11, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Tumor-suppressive activity of sTRAIL on circulating CD44+ cells in patients with non-small cell lung cancer.
Authors: Sun YB, Sun GH, Xu S, Xu JJ Abstract Circulating CD44+ cells have been identified as a prognostic marker for patients with non-small cell lung cancer (NSCLC). Serum tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) is involved in the pathophysiology of many cancers. However, no previous studies have shown the roles of sTRAIL in circulating CD44+ cells in the blood of NSCLC patients. We detected circulating CD44+ cells and sTRAIL levels in blood samples from NSCLC patients using flow cytometry and an enzyme-linked immunosorbent assay (ELISA). Anti-tumor roles of TRAIL in CD44+ cells were conf...
Source: Biological Chemistry - September 27, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Structural investigations of cell-free expressed G protein-coupled receptors.
Authors: Kögler LM, Stichel J, Beck-Sickinger AG Abstract G protein-coupled receptors (GPCRs) are of great pharmaceutical interest and about 35% of the commercial drugs target these proteins. Still there is huge potential left in finding molecules that target new GPCRs or that modulate GPCRs differentially. For a rational drug design, it is important to understand the structure, binding and activation of the protein of interest. Structural investigations of GPCRs remain challenging, although huge progress has been made in the last 20 years, especially in the generation of crystal structures of GPCRs. This is m...
Source: Biological Chemistry - September 21, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Bone marrow-derived mesenchymal stem cells utilize the notch signaling pathway to induce apoptosis of hepatic stellate cells via NF- κB sensor.
Bone marrow-derived mesenchymal stem cells utilize the notch signaling pathway to induce apoptosis of hepatic stellate cells via NF-κB sensor. Biol Chem. 2019 Sep 17;: Authors: Lin N, Yao Z, Xu L, Xu M, Yuan L, Zhuang H, Lin Y, Xu R Abstract The present study aimed at evaluating the mechanism by which functionality of hepatic stellate cells (HSCs) is modulated by bone marrow stromal cells (BMSCs). Induction of apoptosis in HSCs was found to be caused by directly co-culturing HSCs with BMSCs, where the expression of α-smooth muscle actin (α-SMA) increased significantly in HSCs, along w...
Source: Biological Chemistry - September 20, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Highlight: Young research groups in Germany - continued.
Authors: Hennig J, Feige MJ PMID: 31527288 [PubMed - as supplied by publisher] (Source: Biological Chemistry)
Source: Biological Chemistry - September 20, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Coupling of import and assembly pathways in mitochondrial protein biogenesis.
Authors: Grevel A, Pfanner N, Becker T Abstract Biogenesis and function of mitochondria depend on the import of about 1000 precursor proteins that are produced on cytosolic ribosomes. The translocase of the outer membrane (TOM) forms the entry gate for most proteins. After passage through the TOM channel, dedicated preprotein translocases sort the precursor proteins into the mitochondrial subcompartments. Many proteins have to be assembled into oligomeric membrane-integrated complexes in order to perform their functions. In this review, we discuss a dual role of mitochondrial preprotein translocases in protein tran...
Source: Biological Chemistry - September 14, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Direct coupling analysis improves the identification of beneficial amino acid mutations for the functional thermostabilization of a delicate decarboxylase.
Authors: Peng M, Maier M, Esch J, Schug A, Rabe KS Abstract The optimization of enzyme properties for specific reaction conditions enables their tailored use in biotechnology. Predictions using established computer-based methods, however, remain challenging, especially regarding physical parameters such as thermostability without concurrent loss of activity. Employing established computational methods such as energy calculations using FoldX can lead to the identification of beneficial single amino acid substitutions for the thermostabilization of enzymes. However, these methods require a three-dimensional (3D)-stru...
Source: Biological Chemistry - September 1, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Exofacial phospholipids at the plasma membrane: ill-defined targets for early infection processes.
Authors: Galle JN, Hegemann JH Abstract The eukaryotic plasma membrane (PM) consists largely of phospholipids and proteins, and separates the intracellular compartments from the extracellular space. It also serves as a signaling platform for cell-to-cell communication and an interaction platform for the molecular crosstalk between pathogens and their target cells. Much research has been done to elucidate the interactions between pathogens and host membrane proteins. However, little is known about the interactions between pathogens and membrane phospholipids, although reports have described a contribution of phospho...
Source: Biological Chemistry - August 15, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Genetic, epigenetic and biochemical regulation of succinate dehydrogenase function.
Authors: Moosavi B, Zhu XL, Yang WC, Yang GF Abstract Succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP. Impaired function of SDH results in deleterious disorders from cancer to neurodegeneration. SDH function is tailored in different cell types to meet the energy demands. Thus understanding how SDH function is regulated and how it operates in distinct cell types can support the development of therapeutic approaches against the diseases....
Source: Biological Chemistry - August 15, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Emerging mechanisms of drug-induced phospholipidosis.
Authors: Breiden B, Sandhoff K Abstract Drug-induced phospholipidosis is a lysosomal storage disorder characterized by excessive accumulation of phospholipids. Its cellular mechanism is still not well understood, but it is known that cationic amphiphilic drugs can induce it. These drugs have a hydrophilic amine head group that can be protonated in the endolysosomal compartment. As cationic amphiphiles, they are trapped in lysosomes, where they interfere with negatively charged intralysosomal vesicles, the major platforms of cellular sphingolipid degradation. Metabolic principles observed in sphingolipid and phospho...
Source: Biological Chemistry - August 15, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Structure, dynamics, and interactions of large SRP variants.
Authors: Wild K, Becker MMM, Kempf G, Sinning I Abstract Co-translational protein targeting to membranes relies on the signal recognition particle (SRP) system consisting of a cytosolic ribonucleoprotein complex and its membrane-associated receptor. SRP recognizes N-terminal cleavable signals or signal anchor sequences, retards translation, and delivers ribosome - nascent chain complexes (RNCs) to vacant translocation channels in the target membrane. While our mechanistic understanding is well advanced for the small bacterial systems it lags behind for the large bacterial, archaeal, and eukaryotic SRP variants incl...
Source: Biological Chemistry - August 15, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

LncRNA MALAT1 inhibits hypoxia/reoxygenationinduced human umbilical vein endothelial cell injury via targeting the microRNA-320a/RAC1 axis.
Authors: Zhu R, Hu X, Xu W, Wu Z, Zhu Y, Ren Y, Cheng L Abstract Angiogenesis is believed to protect against hypoxia/reoxygenation (H/R)-induced cell injury. MALAT1 and microRNA-320a (miR-320a) are involved in cancer angiogenesis. To investigate the function of the MALAT1/miR-320a axis in H/R-induced cell injury, human umbilical vein endothelial cell (HUVEC) angiogenesis was detected using CCK-8, transwell migration, cell adhesion and tube formation assays. The expression of MALAT1 and miR- 320a was revealed by qRT-PCR. The direct binding relationship between miR-320a and MALAT1 was detected by RNA immunoprecipitat...
Source: Biological Chemistry - August 15, 2019 Category: Chemistry Tags: Biol Chem Source Type: research