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https://www.readbyqxmd.com/read/28098172/structural-diversity-of-anti-pancreatic-cancer-capsimycins-identified-in-mangrove-derived-streptomyces-xiamenensis-318-and-post-modification-via-a-novel-cytochrome-p450-monooxygenase
#1
He-Lin Yu, Shu-Heng Jiang, Xu-Liang Bu, Jia-Hua Wang, Jing-Yi Weng, Xiao-Mei Yang, Kun-Yan He, Zhi-Gang Zhang, Ping Ao, Jun Xu, Min-Juan Xu
Polycyclic tetramate macrolactams (PTMs) were identified as distinct secondary metabolites of the mangrove-derived Streptomyces xiamenensis 318. Together with three known compounds-ikarugamycin (1), capsimycin (2) and capsimycin B (3)-two new compounds, capsimycin C (4) with trans-diols and capsimycin D (5) with trans-configurations at C-13/C-14, have been identified. The absolute configurations of the tert/tert-diols moiety was determined in 4 by NMR spectroscopic analysis, CD spectral comparisons and semi-synthetic method...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28092048/using-reciprocal-protein-peptide-array-screening-to-unravel-protein-interaction-networks
#2
Huadong Liu, Courtney Voss, Shawn S C Li
Protein-protein interactions (PPIs) play a central role in almost all cellular processes. Recent technological advances have enabled the elucidation of an incredibly complex PPI network within the cell. However, protein interactions driven by posttranslational modifications (PTMs) such as phosphorylation, which comprises a significant part of the PPI network, have proven difficult to decipher systematically. Herein, we describe a reciprocal protein-peptide array strategy to uncover PPIs mediated by tyrosine phosphorylation and the Src homology 2 (SH2) domain...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28079948/induction-of-antibodies-directed-against-branched-core-o-mannosyl-glycopeptides-selectivity-complimentary-to-the-cona-lectin
#3
Jin Yu, Oliver C Grant, Christian Pett, Sabine Strahl, Robert J Woods, Ulrika Westerlind
Mammalian protein O-mannosylation comprise a group of post-translational modifications (PTMs) involved in muscle and brain development. Despite the enormous progress made, to date the biological impact of the mammalian O-mannosyl glycoproteome remains largely unknown. Tools are still needed to investigate the structure, role and abundance of O-mannosyl glycans. While O-mannosyl branching has been shown to be of relevance in integrin-dependent cell-migration, and also plays a role in demyelinating diseases, a broader understanding of the biological roles of branched O-mannosyl glycans is lacking in part due to the paucity of detection tools...
January 12, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28079009/emerging-roles-of-calreticulin-in-cancer-implications-for-therapy
#4
Kavya Venkateswaran, Amit Verma, Anant Narayan Bhatt, Anju Shrivastava, Kailash Manda, Hanumantharao G Raj, Ashok Prasad, Christophe Len, Virinder S Parmar, Bilikere Dwarakanath
Calreticulin (CRT), initially identified as a ubiquitous calcium-binding protein in the endoplasmic reticulum, has emerged as a multifunctional protein with roles in calcium homeostasis, molecular chaperoning and cell adhesion. Emerging evidence suggests its involvement in tumorigenesis facilitating proliferation, migration, and adhesion. CRT translocated to the cell surface (ecto-CRT) serves as a phagocytic signal for immunogenic cell death (ICD) mediated through dendritic cells (DCs) and cytotoxic T-cell activation thereby making tumors susceptible to immunotherapy-based anti-cancer strategies...
January 11, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28078386/early-differences-in-islets-from-prediabetic-nod-mice-combined-microarray-and-proteomic-analysis
#5
Inne Crèvecoeur, Valborg Gudmundsdottir, Saurabh Vig, Fernanda Marques Câmara Sodré, Wannes D'Hertog, Ana Carolina Fierro, Leentje Van Lommel, Conny Gysemans, Kathleen Marchal, Etienne Waelkens, Frans Schuit, Søren Brunak, Lut Overbergh, Chantal Mathieu
AIMS/HYPOTHESIS: Type 1 diabetes is an endocrine disease where a long preclinical phase, characterised by immune cell infiltration in the islets of Langerhans, precedes elevated blood glucose levels and disease onset. Although several studies have investigated the role of the immune system in this process of insulitis, the importance of the beta cells themselves in the initiation of type 1 diabetes is less well understood. The aim of this study was to investigate intrinsic differences present in the islets from diabetes-prone NOD mice before the onset of insulitis...
January 12, 2017: Diabetologia
https://www.readbyqxmd.com/read/28071717/tryptophan-and-non-tryptophan-fluorescence-of-the-eye-lens-proteins-provides-diagnostics-of-cataract-at-the-molecular-level
#6
Anna Gakamsky, Rory R Duncan, Nicola M Howarth, Baljean Dhillon, Kim K Buttenschön, Daniel J Daly, Dmitry Gakamsky
The chemical nature of the non-tryptophan (non-Trp) fluorescence of porcine and human eye lens proteins was identified by Mass Spectrometry (MS) and Fluorescence Steady-State and Lifetime spectroscopy as post-translational modifications (PTM) of Trp and Arg amino acid residues. Fluorescence intensity profiles measured along the optical axis of human eye lenses with age-related nuclear cataract showed increasing concentration of fluorescent PTM towards the lens centre in accord with the increased optical density in the lens nucleolus...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28067280/increase-in-%C3%AE-tubulin-modifications-in-the-neuronal-processes-of-hippocampal-neurons-in-both-kainic-acid-induced-epileptic-seizure-and-alzheimer-s-disease
#7
Hang Thi Vu, Hiroyasu Akatsu, Yoshio Hashizume, Mitsutoshi Setou, Koji Ikegami
Neurodegeneration includes acute changes and slow-developing alterations, both of which partly involve common cellular machinery. During neurodegeneration, neuronal processes are impaired along with dysregulated post-translational modifications (PTMs) of cytoskeletal proteins. In neuronal processes, tubulin undergoes unique PTMs including a branched form of modification called glutamylation and loss of the C-terminal tyrosine residue and the penultimate glutamic acid residue forming Δ2-tubulin. Here, we investigated the state of two PTMs, glutamylation and Δ2 form, in both acute and slow-developing neurodegenerations, using a newly generated monoclonal antibody, DTE41, which had 2-fold higher affinity to glutamylated Δ2-tubulin, than to unmodified Δ2-tubulin...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28065793/polyglutamine-expansion-of-ataxin-3-alters-its-degree-of-ubiquitination-and-phosphorylation-at-specific-sites
#8
Line V Kristensen, Felix S Oppermann, Matthias J Rauen, Rasmus Hartmann-Petersen, Kenneth Thirstrup
Ubiquitination and phosphorylation of proteins represent post translational modifications (PTMs) capable of regulating a variety of cellular processes. In the neurodegenerative disorder spinocerebellar ataxia type 3 (SCA3), the disease causing protein ataxin-3 carries an expanded polyglutamine (polyQ) stretch causing it to aggregate in nuclear inclusions. These inclusions are decorated with ubiquitin suggestive of a malfunction in the clearance of the mutant protein. Differences in ubiquitin chain topology between normal and polyQ expanded ataxin-3 could be involved in the differential clearance of the two proteins and play a role in SCA3 pathogenesis...
January 5, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28045584/epigenetic-countermarks-in-mitotic-chromosome-condensation
#9
Karel H M van Wely, Carmen Mora Gallardo, Kendra R Vann, Tatiana G Kutateladze
Mitosis in metazoans is characterized by abundant phosphorylation of histone H3 and involves the recruitment of condensin complexes to chromatin. The relationship between the 2 phenomena and their respective contributions to chromosome condensation in vivo remain poorly understood. Recent studies have shown that H3T3 phosphorylation decreases binding of histone readers to methylated H3K4 in vitro and is essential to displace the corresponding proteins from mitotic chromatin in vivo. Together with previous observations, these data provide further evidence for a role of mitotic histone H3 phosphorylation in blocking transcriptional programs or preserving the 'memory' PTMs...
January 3, 2017: Nucleus
https://www.readbyqxmd.com/read/28034318/sensitive-and-precise-characterization-of-combinatorial-histone-modifications-by-selective-derivatization-coupled-with-rplc-ethcd-ms-ms
#10
Rijing Liao, Dan Zheng, Aiying Nie, Shaolian Zhou, Haibing Deng, Yuan Gao, Pengyuan Yang, Yanyan Yu, Lin Tan, Wei Qi, Jiaxi Wu, En Li, Wei Yi
Deciphering the combinatorial histone codes has been a long-standing interest in the epigenetics field, which requires the reliable and robust characterization of the post-translational modifications (PTMs) coexisting on histones. To this end, weak cation exchange hydrophilic interaction liquid chromatography is commonly used in middle-down liquid chromatography-mass spectrometry approaches for online separation of variously modified histone peptides. Here we provide a novel strategy that combines the selective histone peptide derivatization using N-hydroxysuccinimide propionate ester with reversed-phase liquid chromatography (RPLC) for the robust, sensitive, and reliable characterization of combinatorial histone PTMs...
January 11, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28032848/the-chd1-chromatin-remodeler-shifts-hexasomes-unidirectionally
#11
Robert F Levendosky, Anton Sabantsev, Sebastian Deindl, Gregory D Bowman
Despite their canonical two-fold symmetry, nucleosomes in biological contexts are often asymmetric: functionalized with post-translational modifications (PTMs), substituted with histone variants, and even lacking H2A/H2B dimers. Here we show that the Widom 601 nucleosome positioning sequence can produce hexasomes in a specific orientation on DNA, providing a useful tool for interrogating chromatin enzymes and allowing for the generation of nucleosomes with precisely defined asymmetry. Using this methodology, we demonstrate that the Chd1 chromatin remodeler from Saccharomyces cerevisiae requires H2A/H2B on the entry side for sliding, and thus, unlike the back-and-forth sliding observed for nucleosomes, Chd1 shifts hexasomes unidirectionally...
December 29, 2016: ELife
https://www.readbyqxmd.com/read/28029071/predicting-citrullination-sites-in-protein-sequences-using-mrmr-method-and-random-forest-algorithm
#12
Qing Zhang, Xijun Sun, Kaiyan Feng, ShaoPeng Wang, Yu-Hang Zhang, SiBao Wang, Lin Lu, Yu-Dong Cai
As one of essential post-translational modifications (PTMs), the citrullination or deimination on an arginine residue would change the molecular weight and electrostatic charge of its side-chain. And it has been found that the citrullination in protein sequences was catalyzed by a type of Ca2+-dependent enzyme family called peptidylarginine deiminase (PAD), which include five isotypes: PAD1, 2, 3, 4/5, and 6. Citrullinated proteins participate in many biological processes, e.g. the citrullination of myelin basic protein (MBP) assists the early development of central nervous system...
December 27, 2016: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28025335/caspneurod-a-knowledgebase-of-predicted-caspase-cleavage-sites-in-human-proteins-related-to-neurodegenerative-diseases
#13
Sonu Kumar, Piotr Cieplak
BACKGROUND: A variety of neurodegenerative diseases (NDs) have been associated with deregulated caspase activation that leads to neuronal death. Caspases appear to be involved in the molecular pathology of NDs by directly cleaving important proteins. For instance, several proteins involved in Alzheimer's disease, including β-amyloid precursor protein (APP) and presenilins, are known to be cleaved by caspases. Therefore, cell death pathway may play a central role in many neurological diseases, and targeting the important proteins that control the cell survival and death may potentially represent a therapeutic approach for chronic neurodegenerative disorders...
2016: Database: the Journal of Biological Databases and Curation
https://www.readbyqxmd.com/read/28025199/computational-prediction-of-species-specific-malonylation-sites-via-enhanced-characteristic-strategy
#14
Li-Na Wang, Shao-Ping Shi, Hao-Dong Xu, Ping-Ping Wen, Jian-Ding Qiu
MOTIVATION: Protein malonylation is a novel post-translational modification (PTM) which orchestrates a variety of biological processes. Annotation of malonylation in proteomics is the first-crucial step to decipher its physiological roles which are implicated in the pathological processes. Comparing with the expensive and laborious experimental research, computational prediction can provide an accurate and effective approach to the identification of many types of PTMs sites. However, there is still no online predictor for lysine malonylation...
December 23, 2016: Bioinformatics
https://www.readbyqxmd.com/read/28025033/using-comparative-biology-to-understand-how-aging-affects-mitochondrial-metabolism
#15
Rashpal S Dhillon, John M Denu
Lifespan varies considerably among even closely related species, as exemplified by rodents and primates. Despite these disparities in lifespan, most studies have focused on intra-specific aging pathologies, primarily within a select few systems. While mice have provided much insight into aging biology, it is unclear if such a short-lived species lack defences against senescence that may have evolved in related longevous species. Many age-related diseases have been linked to mitochondrial dysfunction that are measured by decreased energy generation, structural damage to cellular components, and even cell death...
December 23, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28017137/effects-of-crosstalk-between-sumoylation-and-phosphorylation-in-normal-cellular-physiology-and-human-diseases
#16
Q Nie, X-D Gong, M Liu, D W-C Li
Post-translational modifications (PTMs) such as phosphorylation, acetylation, methylation, ubiquitylation, sumoylation are important mechanisms to regulate the functions of different proteins. Among various PTMs, phosphorylation, discovered about 60 years ago, is probably the most common modification. In contrast, sumoylation, identified about two decades is emerging as a key regulatory mechanism modulating protein functions. Although studies on protein phosphorylation and sumoylation have been extensively reviewed, much less attention has been paid to their cross-talk and their co-regulation of the same protein target...
December 22, 2016: Current Molecular Medicine
https://www.readbyqxmd.com/read/28017135/role-of-sumoylation-in-heart-development-and-cardiovascular-diseases
#17
L Zhang, T-H Yang, D W-C Li
Heart is an extremely important organ, and cardiovascular disorders emerge as primary life-threatening disease in human life. Aberrant post-translational modifications (PTMs) on cardiac proteins are closely correlated with pathological abnormalities in heart. SUMOylation, one of the most prevalent PTMs with thousands of substrates throughout the cell including critical subcellular organelles, has been shown to precisely fine-tune the cell survival and proliferation during heart development, and delicately control the function of mitochondrion and sarcoplasmic reticulum in physiological heart functioning...
December 23, 2016: Current Molecular Medicine
https://www.readbyqxmd.com/read/28011818/the-emerging-complexity-of-ubiquitin-architecture
#18
Fumiaki Ohtake, Hikaru Tsuchiya
Ubiquitylation is an essential post-translational modification (PTM) of proteins with diverse cellular functions. Polyubiquitin chains with different topologies have different cellular roles, and are referred to as a 'ubiquitin code'. Recent studies have begun to reveal that more complex ubiquitin architectures function as important signals in several biological pathways. These include PTMs of ubiquitin itself, such as acetylated ubiquitin and phospho-ubiquitin. Moreover, important roles for heterogeneous polyubiquitin chains, such as mixed or branched chains, have been reported, which significantly increase the diversity of the ubiquitin code...
December 23, 2016: Journal of Biochemistry
https://www.readbyqxmd.com/read/28003186/posttranslational-modifications-of-tubulin-and-cilia
#19
Dorota Wloga, Ewa Joachimiak, Panagiota Louka, Jacek Gaertig
Tubulin undergoes several highly conserved posttranslational modifications (PTMs) including acetylation, detyrosination, glutamylation, and glycylation. These PTMs accumulate on a subset of microtubules that are long-lived, including those in the basal bodies and axonemes. Tubulin PTMs are distributed nonuniformly. In the outer doublet microtubules of the axoneme, the B-tubules are highly enriched in the detyrosinated, polyglutamylated, and polyglycylated tubulin, whereas the A-tubules contain mostly unmodified tubulin...
December 21, 2016: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28001079/profiling-of-histone-post-translational-modifications-in-mouse-brain-with-high-resolution-top-down-mass-spectrometry
#20
Mowei Zhou, Ljiljana Paša-Tolić, David L Stenoien
As histones play central roles in most chromosomal functions including regulation of DNA replication, DNA damage repair, and gene transcription, both their basic biology and their roles in disease development have been the subject of intense study. Because multiple post-translational modifications (PTMs) along the entire protein sequence are potential regulators of histones, a top-down approach, where intact proteins are analyzed, is ultimately required for complete characterization of proteoforms. However, significant challenges remain for top-down histone analysis primarily because of deficiencies in separation/resolving power and effective identification algorithms...
December 21, 2016: Journal of Proteome Research
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